Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number

Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship i...

Full description

Saved in:
Bibliographic Details
Published inPLoS biology Vol. 15; no. 11; p. e2002429
Main Authors Katsanos, Dimitris, Koneru, Sneha L., Mestek Boukhibar, Lamia, Gritti, Nicola, Ghose, Ritobrata, Appleford, Peter J., Doitsidou, Maria, Woollard, Alison, van Zon, Jeroen S., Poole, Richard J., Barkoulas, Michalis
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 06.11.2017
Public Library of Science (PLoS)
Subjects
Animals
Biochemistry
Biology and Life Sciences
Caenorhabditis elegans
Caenorhabditis elegans - genetics
Caenorhabditis elegans - growth & development
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Cell Count
Cell Differentiation
Cell Division
Cell Lineage
Cell number
Cells, Cultured
CRISPR
Data collection
Developmental biology
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Epidermal Cells
Epidermis
Epidermis - metabolism
Feasibility studies
Gene expression
Gene Expression Regulation
Genetic variability
Genetics
Genomes
Helix-loop-helix proteins
Helix-loop-helix proteins (basic)
Life sciences
Molecular physics
Mutagenesis
Mutants
Mutation
Nematodes
Physiological aspects
Research and Analysis Methods
Screens
Signal transduction
Signaling
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Stochastic Processes
Stochasticity
Transcription factors
Transcription Factors - genetics
Transcription Factors - metabolism
University colleges
Variability
Wnt protein
Wnt Signaling Pathway
Online AccessGet full text
ISSN1545-7885
1544-9173
1545-7885
DOI10.1371/journal.pbio.2002429

Cover

Abstract Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens.
AbstractList Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens.
Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens.Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens.
Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22 , a Hes -related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens. Organisms are exposed to both internal and external perturbations in every molecular process they go through, and robustness—the ability to maintain their systems unchanged—is crucial for their development and survival. However, the processes that keep the variability of cells as low as possible are barely known. The nematode C . elegans is notable for its highly reproducible development, showing an almost invariant pattern of cell division and differentiation during development; it is thus an ideal model organism in which to search for genes that regulate phenotypic consistency among genetically identical individuals. We focus on a group of lateral epidermal cells—the seam cells—which undergo stem cell-like divisions during postembryonic development. These divisions can either be symmetric towards the seam cell fate, acting to increase the total number of cells, or asymmetric, giving rise to one daughter cell that differentiates into its final fate and another one that serves to keep the number of seam cells constant. We show here that mutations in the transcription factor lin-22 increase seam cell number variability due to stochastic conversion of symmetric divisions into asymmetric ones and vice versa during development, thereby altering the number of terminal seam cell number in opposing directions. We also show that the observed phenotypic variability correlates with the stochastic activation of the conserved Wnt signaling pathway. Our work suggests that core components of developmental gene networks modulate phenotypic variability in multicellular animals.
Audience Academic
Author Katsanos, Dimitris
Doitsidou, Maria
Gritti, Nicola
Appleford, Peter J.
Mestek Boukhibar, Lamia
Ghose, Ritobrata
Barkoulas, Michalis
Koneru, Sneha L.
van Zon, Jeroen S.
Woollard, Alison
Poole, Richard J.
AuthorAffiliation New York University, United States of America
4 Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom
3 Department of Biochemistry, University of Oxford, Oxford, United Kingdom
2 Institute for Atomic and Molecular Physics (AMOLF), Amsterdam, The Netherlands
1 Department of Life Sciences, Imperial College, London, United Kingdom
5 Department of Cell and Developmental Biology, University College London, London, United Kingdom
AuthorAffiliation_xml – name: 3 Department of Biochemistry, University of Oxford, Oxford, United Kingdom
– name: 5 Department of Cell and Developmental Biology, University College London, London, United Kingdom
– name: 4 Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom
– name: 2 Institute for Atomic and Molecular Physics (AMOLF), Amsterdam, The Netherlands
– name: New York University, United States of America
– name: 1 Department of Life Sciences, Imperial College, London, United Kingdom
Author_xml – sequence: 1
  givenname: Dimitris
  surname: Katsanos
  fullname: Katsanos, Dimitris
– sequence: 2
  givenname: Sneha L.
  surname: Koneru
  fullname: Koneru, Sneha L.
– sequence: 3
  givenname: Lamia
  surname: Mestek Boukhibar
  fullname: Mestek Boukhibar, Lamia
– sequence: 4
  givenname: Nicola
  surname: Gritti
  fullname: Gritti, Nicola
– sequence: 5
  givenname: Ritobrata
  surname: Ghose
  fullname: Ghose, Ritobrata
– sequence: 6
  givenname: Peter J.
  surname: Appleford
  fullname: Appleford, Peter J.
– sequence: 7
  givenname: Maria
  surname: Doitsidou
  fullname: Doitsidou, Maria
– sequence: 8
  givenname: Alison
  surname: Woollard
  fullname: Woollard, Alison
– sequence: 9
  givenname: Jeroen S.
  surname: van Zon
  fullname: van Zon, Jeroen S.
– sequence: 10
  givenname: Richard J.
  surname: Poole
  fullname: Poole, Richard J.
– sequence: 11
  givenname: Michalis
  orcidid: 0000-0003-1974-7668
  surname: Barkoulas
  fullname: Barkoulas, Michalis
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29108019$$D View this record in MEDLINE/PubMed
BookMark eNqVk9tu1DAQhiNURA_wBggscQMXu9jOwTEXSNWKw0oVlShwaznOZNerJN7aTkXfngmbRd2qQqBcOJr55rfn18xpctS7HpLkOaNzlgr2duMG3-t2vq2sm3NKecblo-SE5Vk-E2WZH935P05OQ9ggwyUvnyTHXDJaUiZPknAVnVnrEK0hrQuB6L4mK2174hoSbrsOosdUbW9ssK4PBDNxDWQxJ9DCSmMEtrYG39lAtuDj4KtAvKuGEHtAvVEmQkcMtC3ph64C_zR53Og2wLPpPEu-f_zwbfF5dnH5abk4v5gZUbA4qxiDusloKnKNLwctGpllupBCNkUqpRCa0wY48NxkmleN5E1a05zpMjV5pdOz5OVOd4udqcmvoJgsJWUlzQskljuidnqjtt522t8qp636HXB-pbRHa1pQBRcip6WpMlFnXKQyr3nBS60rUza0KFHr_XTbUHVQG-ij1-2B6GGmt2u1cjcqLyTWjwKvJwHvrgcIUaGno226BzeM7y5YkWaCSURf3UMf7m6iVhobsH3j8F4ziqrznBWiEFQKpOYPUPjV0FmDM9dYjB8UvDkoQCbCz7jSQwhqefX1P9gv_85e_jhkX9w1-4_L-8FG4N0OMB6n2kOjjI064ghjd7ZVjKpxi_a-qXGL1LRFWJzdK97r_7XsF40UINk
CitedBy_id crossref_primary_10_3389_fgene_2018_00382
crossref_primary_10_1111_nph_19334
crossref_primary_10_1038_s41467_021_23567_1
crossref_primary_10_1002_jez_2254
crossref_primary_10_1038_s41598_021_88500_4
crossref_primary_10_1371_journal_pgen_1010209
crossref_primary_10_1534_genetics_119_302896
crossref_primary_10_3389_fcell_2021_640856
crossref_primary_10_1016_j_ydbio_2024_09_014
crossref_primary_10_7554_eLife_46703
crossref_primary_10_1016_j_celrep_2020_108604
crossref_primary_10_7554_eLife_63265
crossref_primary_10_3390_ijms19103029
crossref_primary_10_1093_gerona_glab045
crossref_primary_10_1093_genetics_iyad174
crossref_primary_10_1038_s41477_020_0666_7
crossref_primary_10_1242_dev_204546
crossref_primary_10_3389_fgene_2018_00523
crossref_primary_10_1016_j_isci_2025_111826
crossref_primary_10_1242_dev_199452
crossref_primary_10_1093_genetics_iyae207
crossref_primary_10_1126_sciadv_abk3141
Cites_doi 10.1371/journal.pone.0015435
10.1038/nmeth.1253
10.1038/nmeth.1923
10.1073/pnas.042497999
10.1038/nrg3949
10.1534/genetics.112.144204
10.1016/j.ydbio.2011.06.006
10.1186/gb-2010-11-10-r106
10.1093/aob/mcv128
10.1126/science.aaf7012
10.1016/j.tig.2009.07.005
10.1038/ncomms12500
10.1101/gad.9.24.3136
10.1242/dev.116.2.457
10.1371/journal.pgen.1002308
10.1242/dev.008276
10.1016/j.cell.2013.09.060
10.1038/35014651
10.1186/1752-0509-7-54
10.1534/genetics.114.169730
10.1016/j.devcel.2009.02.011
10.1242/dev.000786
10.1016/j.devcel.2016.06.016
10.7554/eLife.16118
10.1016/j.ydbio.2010.09.005
10.1371/journal.pgen.1002314
10.1371/journal.pgen.1005099
10.1073/pnas.1422852112
10.1242/dev.128.15.2867
10.1371/journal.pbio.0060264
10.1073/pnas.1013148108
10.1093/genetics/146.1.185
10.1016/S1534-5807(02)00129-6
10.1002/wdev.79
10.1073/pnas.0701936104
10.1016/j.ydbio.2015.04.025
10.1073/pnas.96.21.11883
10.1371/journal.pbio.2000465
10.1016/j.celrep.2012.05.017
10.1038/nature10665
10.1093/genetics/77.1.71
10.1016/j.copbio.2013.03.010
10.1016/0012-1606(77)90158-0
10.1038/nature01765
10.1242/dev.091124
10.1242/dev.124.15.2875
10.1093/bioinformatics/btq033
10.1371/journal.pgen.1002839
10.1016/S0092-8674(00)80917-4
10.1016/j.tcb.2007.08.004
10.1016/j.devcel.2008.09.011
10.1371/journal.pgen.1002200
10.1101/SQB.1983.048.01.050
10.1038/150563a0
10.1016/B978-0-12-396968-2.00006-3
10.1016/j.molcel.2016.05.023
10.1038/46211
10.1073/pnas.1503830112
10.1126/science.1242366
10.1371/journal.pone.0017650
10.1016/j.jtbi.2008.07.013
10.1080/15384047.2015.1016662
10.1038/nrg1471
10.1126/science.1240276
10.1016/0012-1606(88)90414-9
10.1016/j.cub.2006.06.058
10.1534/g3.113.006999
10.1016/j.devcel.2012.12.001
10.1038/24550
10.1038/msb.2013.53
10.1038/nature08781
10.1038/nmeth.2532
10.1371/journal.pgen.1002295
10.1242/dev.129.2.443
10.1371/journal.pgen.1000049
10.1126/science.1250220
10.1371/journal.pgen.1004133
10.1534/genetics.115.186197
10.1242/dev.126.4.805
10.15252/msb.20145264
10.1101/gad.1823109
10.1111/mec.12091
10.1016/0092-8674(95)90100-0
10.1126/science.1074560
10.1111/j.1558-5646.2012.01636.x
ContentType Journal Article
Copyright COPYRIGHT 2017 Public Library of Science
2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: epidermis perturbs robustness of stem cell number. PLoS Biol 15(11): e2002429. https://doi.org/10.1371/journal.pbio.2002429
2017 Katsanos et al 2017 Katsanos et al
2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: epidermis perturbs robustness of stem cell number. PLoS Biol 15(11): e2002429. https://doi.org/10.1371/journal.pbio.2002429
Copyright_xml – notice: COPYRIGHT 2017 Public Library of Science
– notice: 2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: epidermis perturbs robustness of stem cell number. PLoS Biol 15(11): e2002429. https://doi.org/10.1371/journal.pbio.2002429
– notice: 2017 Katsanos et al 2017 Katsanos et al
– notice: 2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: epidermis perturbs robustness of stem cell number. PLoS Biol 15(11): e2002429. https://doi.org/10.1371/journal.pbio.2002429
DBID AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
IOV
ISN
ISR
3V.
7QG
7QL
7SN
7SS
7T5
7TK
7TM
7X7
7XB
88E
8FD
8FE
8FH
8FI
8FJ
8FK
ABUWG
AEUYN
AFKRA
ATCPS
AZQEC
BBNVY
BENPR
BHPHI
C1K
CCPQU
DWQXO
FR3
FYUFA
GHDGH
GNUQQ
H94
HCIFZ
K9.
LK8
M0S
M1P
M7N
M7P
P64
PATMY
PHGZM
PHGZT
PIMPY
PJZUB
PKEHL
PPXIY
PQEST
PQGLB
PQQKQ
PQUKI
PRINS
PYCSY
RC3
7X8
5PM
DOA
CZG
DOI 10.1371/journal.pbio.2002429
DatabaseName CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
Gale In Context: Opposing Viewpoints
Canada in Context
Gale In Context: Science
ProQuest Central (Corporate)
Animal Behavior Abstracts
Bacteriology Abstracts (Microbiology B)
Ecology Abstracts
Entomology Abstracts (Full archive)
Immunology Abstracts
Neurosciences Abstracts
Nucleic Acids Abstracts
Health & Medical Collection
ProQuest Central (purchase pre-March 2016)
Medical Database (Alumni Edition)
Technology Research Database
ProQuest SciTech Collection
ProQuest Natural Science Collection
Hospital Premium Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
ProQuest Central (Alumni)
ProQuest One Sustainability
ProQuest Central UK/Ireland
Agricultural & Environmental Science Collection
ProQuest Central Essentials
Biological Science Collection
ProQuest Central
Natural Science Collection
Environmental Sciences and Pollution Management
ProQuest One
ProQuest Central
Engineering Research Database
Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Central Student
AIDS and Cancer Research Abstracts
SciTech Premium Collection
ProQuest Health & Medical Complete (Alumni)
Biological Sciences
ProQuest Health & Medical Collection
PML(ProQuest Medical Library)
Algology Mycology and Protozoology Abstracts (Microbiology C)
Biological Science Database
Biotechnology and BioEngineering Abstracts
Environmental Science Database
ProQuest Central Premium
ProQuest One Academic
ProQuest Publicly Available Content
ProQuest Health & Medical Research Collection
ProQuest One Academic Middle East (New)
ProQuest One Health & Nursing
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
Environmental Science Collection
Genetics Abstracts
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Open Access Full Text
PLoS Biology
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
Publicly Available Content Database
ProQuest Central Student
ProQuest Central Essentials
Nucleic Acids Abstracts
SciTech Premium Collection
ProQuest Central China
Environmental Sciences and Pollution Management
ProQuest One Applied & Life Sciences
ProQuest One Sustainability
Health Research Premium Collection
Natural Science Collection
Health & Medical Research Collection
Biological Science Collection
ProQuest Central (New)
ProQuest Medical Library (Alumni)
ProQuest Biological Science Collection
ProQuest One Academic Eastern Edition
ProQuest Hospital Collection
Health Research Premium Collection (Alumni)
Biological Science Database
Ecology Abstracts
Neurosciences Abstracts
ProQuest Hospital Collection (Alumni)
Biotechnology and BioEngineering Abstracts
Environmental Science Collection
Entomology Abstracts
ProQuest Health & Medical Complete
ProQuest One Academic UKI Edition
Environmental Science Database
Engineering Research Database
ProQuest One Academic
ProQuest One Academic (New)
Technology Research Database
ProQuest One Academic Middle East (New)
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
ProQuest One Community College
ProQuest One Health & Nursing
ProQuest Natural Science Collection
ProQuest Central
ProQuest Health & Medical Research Collection
Genetics Abstracts
Health and Medicine Complete (Alumni Edition)
ProQuest Central Korea
Bacteriology Abstracts (Microbiology B)
Algology Mycology and Protozoology Abstracts (Microbiology C)
Agricultural & Environmental Science Collection
AIDS and Cancer Research Abstracts
ProQuest SciTech Collection
ProQuest Medical Library
Animal Behavior Abstracts
Immunology Abstracts
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList
MEDLINE
MEDLINE - Academic



Publicly Available Content Database
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
– sequence: 4
  dbid: BENPR
  name: ProQuest Central
  url: https://www.proquest.com/central
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
DocumentTitleAlternate Stem cell robustness to noise in C. elegans
EISSN 1545-7885
ExternalDocumentID 1989018056
oai_doaj_org_article_6277508cb47d427395d2628aabc8f068
PMC5690688
A516767097
29108019
10_1371_journal_pbio_2002429
Genre Journal Article
GrantInformation_xml – fundername: Biotechnology and Biological Sciences Research Council
  grantid: BB/G018448/1
– fundername: NIH HHS
  grantid: P40 OD010440
– fundername: Wellcome Trust
  grantid: 207483/Z/17/Z
GroupedDBID ---
123
29O
2WC
36B
53G
5VS
7X7
7XC
88E
8FE
8FH
8FI
8FJ
AAFWJ
AAUCC
AAWOE
AAYXX
ABDBF
ABIVO
ABUWG
ACGFO
ACIHN
ACPRK
ACUHS
ADBBV
ADRAZ
AEAQA
AENEX
AEUYN
AFKRA
AFPKN
AFRAH
AFXKF
AHMBA
AKRSQ
ALIPV
ALMA_UNASSIGNED_HOLDINGS
AOIJS
ATCPS
B0M
BAWUL
BBNVY
BCNDV
BENPR
BHPHI
BPHCQ
BVXVI
BWKFM
CCPQU
CITATION
CS3
DIK
DU5
E3Z
EAD
EAP
EAS
EBD
EBS
EJD
EMB
EMK
EMOBN
EPL
ESX
F5P
FPL
FYUFA
GROUPED_DOAJ
GX1
HCIFZ
HMCUK
HYE
IAG
IAO
IGS
IHR
IOV
ISE
ISN
ISR
ITC
KQ8
LK8
M1P
M48
M7P
O5R
O5S
OK1
OVT
P2P
PATMY
PHGZM
PHGZT
PIMPY
PQQKQ
PROAC
PSQYO
PV9
PYCSY
QF4
QN7
RNS
RPM
RZL
SJN
SV3
TR2
TUS
UKHRP
WOW
XSB
YZZ
~8M
.GJ
ADXHL
C1A
CGR
CUY
CVF
ECM
EIF
IPNFZ
NPM
PJZUB
PPXIY
PQGLB
RIG
WOQ
PMFND
3V.
7QG
7QL
7SN
7SS
7T5
7TK
7TM
7XB
8FD
8FK
AZQEC
C1K
DWQXO
FR3
GNUQQ
H94
K9.
M7N
P64
PKEHL
PQEST
PQUKI
PRINS
RC3
7X8
5PM
PUEGO
-
AAPBV
ABFLS
ABPTK
ADACO
AGJBV
BBAFP
CZG
M~E
ZA5
ID FETCH-LOGICAL-c761t-b11edf40375a022ea7f944a6979f639977a20fe2e25c4a2bf92f3d051a83c5ba3
IEDL.DBID 7X7
ISSN 1545-7885
1544-9173
IngestDate Fri Nov 26 17:11:53 EST 2021
Wed Aug 27 01:30:42 EDT 2025
Thu Aug 21 18:22:55 EDT 2025
Thu Jul 10 22:19:29 EDT 2025
Fri Jul 25 10:34:17 EDT 2025
Tue Jun 17 22:01:48 EDT 2025
Tue Jun 10 21:02:09 EDT 2025
Fri Jun 27 05:31:38 EDT 2025
Fri Jun 27 05:31:24 EDT 2025
Fri Jun 27 05:30:09 EDT 2025
Mon Jul 21 06:04:07 EDT 2025
Thu Apr 24 23:06:14 EDT 2025
Tue Jul 01 04:20:18 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 11
Language English
License This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Creative Commons Attribution License
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c761t-b11edf40375a022ea7f944a6979f639977a20fe2e25c4a2bf92f3d051a83c5ba3
Notes new_version
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
Current address: Centre for Translational Omics—GOSgene, Genetics and Genomic Medicine, University College London, Institute of Child Health, London, United Kingdom
The authors have declared that no competing interests exist.
ORCID 0000-0003-1974-7668
OpenAccessLink https://www.proquest.com/docview/1989018056?pq-origsite=%requestingapplication%
PMID 29108019
PQID 1989018056
PQPubID 1436341
ParticipantIDs plos_journals_1989018056
doaj_primary_oai_doaj_org_article_6277508cb47d427395d2628aabc8f068
pubmedcentral_primary_oai_pubmedcentral_nih_gov_5690688
proquest_miscellaneous_1961634719
proquest_journals_1989018056
gale_infotracmisc_A516767097
gale_infotracacademiconefile_A516767097
gale_incontextgauss_ISR_A516767097
gale_incontextgauss_ISN_A516767097
gale_incontextgauss_IOV_A516767097
pubmed_primary_29108019
crossref_citationtrail_10_1371_journal_pbio_2002429
crossref_primary_10_1371_journal_pbio_2002429
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2017-11-06
PublicationDateYYYYMMDD 2017-11-06
PublicationDate_xml – month: 11
  year: 2017
  text: 2017-11-06
  day: 06
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: San Francisco
– name: San Francisco, CA USA
PublicationTitle PLoS biology
PublicationTitleAlternate PLoS Biol
PublicationYear 2017
Publisher Public Library of Science
Public Library of Science (PLoS)
Publisher_xml – name: Public Library of Science
– name: Public Library of Science (PLoS)
References CR Bauer (ref23) 2015; 11
T Kobayashi (ref60) 2009; 23
H Momiji (ref70) 2008; 254
L Gorrepati (ref18) 2013; 140
A Bergman (ref58) 2003; 424
MC Hall (ref27) 2007; 104
KA Geiler-Samerotte (ref22) 2013; 24
R Lin (ref48) 1998; 92
M Doitsidou (ref35) 2010; 5
A Raj (ref42) 2008; 5
ZH Liu (ref59) 2015; 16
L Hong (ref57) 2016; 38
AD Chisholm (ref14) 2012; 1
HR Horvitz (ref39) 1983; 48
N Ji (ref65) 2013; 155
S Brenner (ref81) 1974; 77
C Braendle (ref75) 2008; 15
JB Penigault (ref79) 2011; 357
A Wagner (ref5) 2007
LA Wrischnik (ref37) 1997; 124
P Rompolas (ref80) 2016; 352
PW Sternberg (ref64) 1988; 130
A Raj (ref73) 2010; 463
JE Sulston (ref13) 1977; 56
RM Terns (ref34) 1997; 146
T Fukushige (ref54) 1999; 96
AV Ranawade (ref53) 2013; 3
SF Levy (ref6) 2008; 6
R Rinott (ref8) 2011; 108
NE Phillips (ref61) 2016; 5
M Barkoulas (ref76) 2013; 24
B Schlager (ref62) 2006; 16
G Yvert (ref31) 2013; 7
M Doitsidou (ref36) 2016; 204
SL Rutherford (ref10) 1998; 396
V Bertrand (ref66) 2009; 16
J Masel (ref1) 2009; 25
N Rohner (ref9) 2013; 342
A Cunha (ref12) 1999; 402
AE Rougvie (ref20) 2013; 105
CH Waddington (ref4) 1942; 150
SL Rutherford (ref56) 1998; 396
C Brabin (ref17) 2011; 7
I Imayoshi (ref68) 2013; 342
JE Gleason (ref19) 2010; 348
MF Maduro (ref77) 2015; 404
J Ansel (ref7) 2008; 4
JF Ayroles (ref32) 2015; 112
Y Yamamoto (ref52) 2011; 7
R Nass (ref41) 2002; 99
OF Harandi (ref72) 2015; 112
S Anders (ref85) 2010; 11
A Becskei (ref71) 2000; 405
O Symmons (ref3) 2016; 62
JM Jimenez-Gomez (ref28) 2011; 7
M Ishibashi (ref63) 1995; 9
KA Geiler-Samerotte (ref11) 2016; 14
B Bonev (ref67) 2012; 2
K Koh (ref15) 2001; 128
L Mestek Boukhibar (ref78) 2016; 117
CP Hunter (ref45) 1999; 126
C Bhambhani (ref51) 2014; 10
N Gritti (ref44) 2016; 7
S Fehrmann (ref30) 2013; 9
AR Quinlan (ref84) 2010; 26
GZ Wang (ref33) 2011; 6
KR Siegfried (ref49) 2002; 129
R Lin (ref47) 1995; 83
A Burga (ref74) 2011; 480
RD Dar (ref55) 2014; 344
H Hirata (ref69) 2002; 298
G Minevich (ref82) 2012; 192
R Kageyama (ref38) 2007; 134
AE Friedland (ref87) 2013; 10
KH Takahashi (ref26) 2012; 66
H Kitano (ref21) 2004; 5
V Debat (ref24) 2011; 7
MA Felix (ref2) 2015; 16
X Shen (ref29) 2012; 8
KH Takahashi (ref25) 2013; 22
DA Waring (ref40) 1992; 116
K Mizumoto (ref50) 2007; 17
JA Arribere (ref86) 2014; 198
B Langmead (ref83) 2012; 9
H Kagoshima (ref16) 2007; 134
ML Cohen (ref43) 2015; 11
WA Mohler (ref46) 2002; 2
References_xml – volume: 5
  start-page: e15435
  issue: 11
  year: 2010
  ident: ref35
  article-title: C. elegans mutant identification with a one-step whole-genome-sequencing and SNP mapping strategy
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0015435
– year: 2007
  ident: ref5
  article-title: Robustness and Evolvability in Living Systems
– volume: 5
  start-page: 877
  year: 2008
  ident: ref42
  article-title: Imaging individual mRNA molecules using multiple singly labeled probes
  publication-title: Nat Methods
  doi: 10.1038/nmeth.1253
– volume: 9
  start-page: 357
  year: 2012
  ident: ref83
  article-title: Fast gapped-read alignment with Bowtie 2
  publication-title: Nat Methods
  doi: 10.1038/nmeth.1923
– volume: 99
  start-page: 3264
  year: 2002
  ident: ref41
  article-title: Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.042497999
– volume: 16
  start-page: 483
  year: 2015
  ident: ref2
  article-title: Pervasive robustness in biological systems
  publication-title: Nat Rev Genet
  doi: 10.1038/nrg3949
– volume: 192
  start-page: 1249
  year: 2012
  ident: ref82
  article-title: CloudMap: a cloud-based pipeline for analysis of mutant genome sequences
  publication-title: Genetics
  doi: 10.1534/genetics.112.144204
– volume: 357
  start-page: 428
  year: 2011
  ident: ref79
  article-title: High sensitivity of C. elegans vulval precursor cells to the dose of posterior Wnts
  publication-title: Dev Biol
  doi: 10.1016/j.ydbio.2011.06.006
– volume: 11
  start-page: R106
  year: 2010
  ident: ref85
  article-title: Differential expression analysis for sequence count data
  publication-title: Genome Biol
  doi: 10.1186/gb-2010-11-10-r106
– volume: 117
  start-page: 699
  year: 2016
  ident: ref78
  article-title: The developmental genetics of biological robustness
  publication-title: Ann Bot
  doi: 10.1093/aob/mcv128
– volume: 352
  start-page: 1471
  year: 2016
  ident: ref80
  article-title: Spatiotemporal coordination of stem cell commitment during epidermal homeostasis
  publication-title: Science
  doi: 10.1126/science.aaf7012
– volume: 25
  start-page: 395
  year: 2009
  ident: ref1
  article-title: Robustness: mechanisms and consequences
  publication-title: Trends Genet
  doi: 10.1016/j.tig.2009.07.005
– volume: 7
  start-page: 12500
  year: 2016
  ident: ref44
  article-title: Long-term time-lapse microscopy of C. elegans post-embryonic development
  publication-title: Nat Commun
  doi: 10.1038/ncomms12500
– volume: 9
  start-page: 3136
  year: 1995
  ident: ref63
  article-title: Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects
  publication-title: Genes Dev
  doi: 10.1101/gad.9.24.3136
– volume: 116
  start-page: 457
  year: 1992
  ident: ref40
  article-title: Cell signals allow the expression of a pre-existent neural pattern in C. elegans
  publication-title: Development
  doi: 10.1242/dev.116.2.457
– volume: 7
  start-page: e1002308
  issue: 10
  year: 2011
  ident: ref52
  article-title: Multiple Wnts redundantly control polarity orientation in Caenorhabditis elegans epithelial stem cells
  publication-title: PLoS Genet
  doi: 10.1371/journal.pgen.1002308
– volume: 134
  start-page: 3905
  year: 2007
  ident: ref16
  article-title: The C. elegans CBF beta homologue BRO-1 interacts with the Runx factor, RNT-1, to promote stem cell proliferation and self-renewal
  publication-title: Development
  doi: 10.1242/dev.008276
– volume: 155
  start-page: 869
  year: 2013
  ident: ref65
  article-title: Feedback control of gene expression variability in the Caenorhabditis elegans Wnt pathway
  publication-title: Cell
  doi: 10.1016/j.cell.2013.09.060
– volume: 405
  start-page: 590
  year: 2000
  ident: ref71
  article-title: Engineering stability in gene networks by autoregulation
  publication-title: Nature
  doi: 10.1038/35014651
– volume: 7
  start-page: 54
  year: 2013
  ident: ref31
  article-title: Single-cell phenomics reveals intra-species variation of phenotypic noise in yeast
  publication-title: BMC Syst Biol
  doi: 10.1186/1752-0509-7-54
– volume: 198
  start-page: 837
  year: 2014
  ident: ref86
  article-title: Efficient marker-free recovery of custom genetic modifications with CRISPR/Cas9 in Caenorhabditis elegans
  publication-title: Genetics
  doi: 10.1534/genetics.114.169730
– volume: 16
  start-page: 563
  year: 2009
  ident: ref66
  article-title: Linking asymmetric cell division to the terminal differentiation program of postmitotic neurons in C. elegans
  publication-title: Dev Cell
  doi: 10.1016/j.devcel.2009.02.011
– volume: 134
  start-page: 1243
  year: 2007
  ident: ref38
  article-title: The Hes gene family: repressors and oscillators that orchestrate embryogenesis
  publication-title: Development
  doi: 10.1242/dev.000786
– volume: 38
  start-page: 15
  year: 2016
  ident: ref57
  article-title: Variable cell growth yields reproducible organ development through spatiotemporal averaging
  publication-title: Dev Cell
  doi: 10.1016/j.devcel.2016.06.016
– volume: 5
  year: 2016
  ident: ref61
  article-title: Stochasticity in the miR-9/Hes1 oscillatory network can account for clonal heterogeneity in the timing of differentiation
  publication-title: Elife
  doi: 10.7554/eLife.16118
– volume: 348
  start-page: 58
  year: 2010
  ident: ref19
  article-title: Wnt signaling controls the stem cell-like asymmetric division of the epithelial seam cells during C. elegans larval development
  publication-title: Dev Biol
  doi: 10.1016/j.ydbio.2010.09.005
– volume: 7
  start-page: e1002314
  issue: 10
  year: 2011
  ident: ref24
  article-title: Developmental stability: a major role for cyclin G in Drosophila melanogaster
  publication-title: PLoS Genet
  doi: 10.1371/journal.pgen.1002314
– volume: 11
  start-page: e1005099
  issue: 3
  year: 2015
  ident: ref43
  article-title: The GATA factor elt-1 regulates C. elegans developmental timing by promoting expression of the let-7 family microRNAs
  publication-title: PLoS Genet
  doi: 10.1371/journal.pgen.1005099
– volume: 112
  start-page: E287
  year: 2015
  ident: ref72
  article-title: Control of stem cell self-renewal and differentiation by the heterochronic genes and the cellular asymmetry machinery in Caenorhabditis elegans
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1422852112
– volume: 128
  start-page: 2867
  year: 2001
  ident: ref15
  article-title: ELT-5 and ELT-6 are required continuously to regulate epidermal seam cell differentiation and cell fusion in C. elegans
  publication-title: Development
  doi: 10.1242/dev.128.15.2867
– volume: 6
  start-page: e264
  issue: 11
  year: 2008
  ident: ref6
  article-title: Network hubs buffer environmental variation in Saccharomyces cerevisiae
  publication-title: PLoS Biol
  doi: 10.1371/journal.pbio.0060264
– volume: 108
  start-page: 6329
  year: 2011
  ident: ref8
  article-title: Exploring transcription regulation through cell-to-cell variability
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1013148108
– volume: 146
  start-page: 185
  year: 1997
  ident: ref34
  article-title: A deficiency screen for zygotic loci required for establishment and patterning of the epidermis in Caenorhabditis elegans
  publication-title: Genetics
  doi: 10.1093/genetics/146.1.185
– volume: 2
  start-page: 355
  year: 2002
  ident: ref46
  article-title: The type I membrane protein EFF-1 is essential for developmental cell fusion
  publication-title: Dev Cell
  doi: 10.1016/S1534-5807(02)00129-6
– volume: 1
  start-page: 861
  year: 2012
  ident: ref14
  article-title: The Caenorhabditis elegans epidermis as a model skin. I: development, patterning, and growth
  publication-title: Wiley Interdiscip Rev Dev Biol
  doi: 10.1002/wdev.79
– volume: 104
  start-page: 13717
  year: 2007
  ident: ref27
  article-title: Genetics of microenvironmental canalization in Arabidopsis thaliana
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.0701936104
– volume: 404
  start-page: 66
  year: 2015
  ident: ref77
  article-title: MED GATA factors promote robust development of the C. elegans endoderm
  publication-title: Developmental Biology
  doi: 10.1016/j.ydbio.2015.04.025
– volume: 96
  start-page: 11883
  year: 1999
  ident: ref54
  article-title: Direct visualization of the elt-2 gut-specific GATA factor binding to a target promoter inside the living Caenorhabditis elegans embryo
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.96.21.11883
– volume: 14
  start-page: e2000465
  issue: 10
  year: 2016
  ident: ref11
  article-title: Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90
  publication-title: PLoS Biol
  doi: 10.1371/journal.pbio.2000465
– volume: 2
  start-page: 10
  year: 2012
  ident: ref67
  article-title: MicroRNA-9 Modulates Hes1 ultradian oscillations by forming a double-negative feedback loop
  publication-title: Cell Rep
  doi: 10.1016/j.celrep.2012.05.017
– volume: 480
  start-page: 250
  year: 2011
  ident: ref74
  article-title: Predicting mutation outcome from early stochastic variation in genetic interaction partners
  publication-title: Nature
  doi: 10.1038/nature10665
– volume: 77
  start-page: 71
  year: 1974
  ident: ref81
  article-title: The genetics of Caenorhabditis elegans
  publication-title: Genetics
  doi: 10.1093/genetics/77.1.71
– volume: 24
  start-page: 752
  year: 2013
  ident: ref22
  article-title: The details in the distributions: why and how to study phenotypic variability
  publication-title: Curr Opin Biotechnol
  doi: 10.1016/j.copbio.2013.03.010
– volume: 56
  start-page: 110
  year: 1977
  ident: ref13
  article-title: Post-embryonic cell lineages of the nematode, Caenorhabditis elegans
  publication-title: Dev Biol
  doi: 10.1016/0012-1606(77)90158-0
– volume: 424
  start-page: 549
  year: 2003
  ident: ref58
  article-title: Evolutionary capacitance as a general feature of complex gene networks
  publication-title: Nature
  doi: 10.1038/nature01765
– volume: 140
  start-page: 2093
  year: 2013
  ident: ref18
  article-title: C. elegans GATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells
  publication-title: Development
  doi: 10.1242/dev.091124
– volume: 124
  start-page: 2875
  year: 1997
  ident: ref37
  article-title: The role of lin-22, a hairy/enhancer of split homolog, in patterning the peripheral nervous system of C. elegans
  publication-title: Development
  doi: 10.1242/dev.124.15.2875
– volume: 26
  start-page: 841
  year: 2010
  ident: ref84
  article-title: BEDTools: a flexible suite of utilities for comparing genomic features
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btq033
– volume: 8
  start-page: e1002839
  issue: 8
  year: 2012
  ident: ref29
  article-title: Inheritance Beyond Plain Heritability: Variance-Controlling Genes in Arabidopsis thaliana
  publication-title: PLoS Genet
  doi: 10.1371/journal.pgen.1002839
– volume: 92
  start-page: 229
  year: 1998
  ident: ref48
  article-title: POP-1 and anterior-posterior fate decisions in C. elegans embryos
  publication-title: Cell
  doi: 10.1016/S0092-8674(00)80917-4
– volume: 17
  start-page: 465
  year: 2007
  ident: ref50
  article-title: Two betas or not two betas: regulation of asymmetric division by beta-catenin
  publication-title: Trends Cell Biol
  doi: 10.1016/j.tcb.2007.08.004
– volume: 15
  start-page: 714
  year: 2008
  ident: ref75
  article-title: Plasticity and errors of a robust developmental system in different environments
  publication-title: Dev Cell
  doi: 10.1016/j.devcel.2008.09.011
– volume: 7
  start-page: e1002200
  issue: 8
  year: 2011
  ident: ref17
  article-title: The Caenorhabditis elegans GATA factor ELT-1 works through the cell proliferation regulator BRO-1 and the Fusogen EFF-1 to maintain the seam stem-like fate
  publication-title: PLoS Genet
  doi: 10.1371/journal.pgen.1002200
– volume: 48
  start-page: 453
  issue: Pt 2
  year: 1983
  ident: ref39
  article-title: Mutations that affect neural cell lineages and cell fates during the development of the nematode Caenorhabditis elegans
  publication-title: Cold Spring Harb Symp Quant Biol
  doi: 10.1101/SQB.1983.048.01.050
– volume: 150
  start-page: 563
  year: 1942
  ident: ref4
  article-title: Canalization of development and the inheritance of acquired characters
  publication-title: Nature
  doi: 10.1038/150563a0
– volume: 105
  start-page: 153
  year: 2013
  ident: ref20
  article-title: Developmental transitions in C. elegans larval stages
  publication-title: Curr Top Dev Biol
  doi: 10.1016/B978-0-12-396968-2.00006-3
– volume: 62
  start-page: 788
  year: 2016
  ident: ref3
  article-title: What's Luck Got to Do with It: Single Cells, Multiple Fates, and Biological Nondeterminism
  publication-title: Mol Cell
  doi: 10.1016/j.molcel.2016.05.023
– volume: 402
  start-page: 253
  year: 1999
  ident: ref12
  article-title: Variable cell number in nematodes
  publication-title: Nature
  doi: 10.1038/46211
– volume: 112
  start-page: 6706
  year: 2015
  ident: ref32
  article-title: Behavioral idiosyncrasy reveals genetic control of phenotypic variability
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1503830112
– volume: 342
  start-page: 1203
  year: 2013
  ident: ref68
  article-title: Oscillatory control of factors determining multipotency and fate in mouse neural progenitors
  publication-title: Science
  doi: 10.1126/science.1242366
– volume: 6
  start-page: e17650
  issue: 3
  year: 2011
  ident: ref33
  article-title: A Gene's Ability to Buffer Variation Is Predicted by Its Fitness Contribution and Genetic Interactions
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0017650
– volume: 254
  start-page: 784
  year: 2008
  ident: ref70
  article-title: Dissecting the dynamics of the Hes1 genetic oscillator
  publication-title: J Theor Biol
  doi: 10.1016/j.jtbi.2008.07.013
– volume: 16
  start-page: 353
  year: 2015
  ident: ref59
  article-title: Hes1: a key role in stemness, metastasis and multidrug resistance
  publication-title: Cancer Biol Ther
  doi: 10.1080/15384047.2015.1016662
– volume: 5
  start-page: 826
  year: 2004
  ident: ref21
  article-title: Biological robustness
  publication-title: Nat Rev Genet
  doi: 10.1038/nrg1471
– volume: 342
  start-page: 1372
  year: 2013
  ident: ref9
  article-title: Cryptic variation in morphological evolution: HSP90 as a capacitor for loss of eyes in cavefish
  publication-title: Science
  doi: 10.1126/science.1240276
– volume: 130
  start-page: 67
  year: 1988
  ident: ref64
  article-title: lin-17 mutations of Caenorhabditis elegans disrupt certain asymmetric cell divisions
  publication-title: Dev Biol
  doi: 10.1016/0012-1606(88)90414-9
– volume: 16
  start-page: 1386
  year: 2006
  ident: ref62
  article-title: HAIRY-like transcription factors and the evolution of the nematode vulva equivalence group
  publication-title: Curr Biol
  doi: 10.1016/j.cub.2006.06.058
– volume: 3
  start-page: 1363
  year: 2013
  ident: ref53
  article-title: Caenorhabditis elegans histone deacetylase hda-1 is required for morphogenesis of the vulva and LIN-12/Notch-mediated specification of uterine cell fates
  publication-title: G3 (Bethesda)
  doi: 10.1534/g3.113.006999
– volume: 24
  start-page: 64
  year: 2013
  ident: ref76
  article-title: Robustness and epistasis in the C. elegans vulval signaling network revealed by pathway dosage modulation
  publication-title: Dev Cell
  doi: 10.1016/j.devcel.2012.12.001
– volume: 396
  start-page: 336
  year: 1998
  ident: ref10
  article-title: Hsp90 as a capacitator for morphological evolution
  publication-title: Nature
  doi: 10.1038/24550
– volume: 9
  start-page: 695
  year: 2013
  ident: ref30
  article-title: Natural sequence variants of yeast environmental sensors confer cell-to-cell expression variability
  publication-title: Mol Syst Biol
  doi: 10.1038/msb.2013.53
– volume: 463
  start-page: 913
  year: 2010
  ident: ref73
  article-title: Variability in gene expression underlies incomplete penetrance
  publication-title: Nature
  doi: 10.1038/nature08781
– volume: 10
  start-page: 741
  year: 2013
  ident: ref87
  article-title: Heritable genome editing in C. elegans via a CRISPR-Cas9 system
  publication-title: Nat Methods
  doi: 10.1038/nmeth.2532
– volume: 7
  start-page: e1002295
  issue: 9
  year: 2011
  ident: ref28
  article-title: Genomic analysis of QTLs and genes altering natural variation in stochastic noise
  publication-title: PLoS Genet
  doi: 10.1371/journal.pgen.1002295
– volume: 129
  start-page: 443
  year: 2002
  ident: ref49
  article-title: POP-1 controls axis formation during early gonadogenesis in C. elegans
  publication-title: Development
  doi: 10.1242/dev.129.2.443
– volume: 4
  start-page: e1000049
  issue: 4
  year: 2008
  ident: ref7
  article-title: Cell-to-cell Stochastic variation in gene expression is a complex genetic trait
  publication-title: PLoS Genet
  doi: 10.1371/journal.pgen.1000049
– volume: 396
  start-page: 336
  year: 1998
  ident: ref56
  article-title: Hsp90 as a capacitor for morphological evolution
  publication-title: Nature
  doi: 10.1038/24550
– volume: 344
  start-page: 1392
  year: 2014
  ident: ref55
  article-title: Screening for noise in gene expression identifies drug synergies
  publication-title: Science
  doi: 10.1126/science.1250220
– volume: 10
  start-page: e1004133
  issue: 2
  year: 2014
  ident: ref51
  article-title: Distinct DNA binding sites contribute to the TCF transcriptional switch in C. elegans and Drosophila
  publication-title: PLoS Genet
  doi: 10.1371/journal.pgen.1004133
– volume: 204
  start-page: 451
  year: 2016
  ident: ref36
  article-title: Next-Generation Sequencing-Based Approaches for Mutation Mapping and Identification in Caenorhabditis elegans
  publication-title: Genetics
  doi: 10.1534/genetics.115.186197
– volume: 126
  start-page: 805
  year: 1999
  ident: ref45
  article-title: Hox gene expression in a single Caenorhabditis elegans cell is regulated by a caudal homolog and intercellular signals that inhibit wnt signaling
  publication-title: Development
  doi: 10.1242/dev.126.4.805
– volume: 11
  start-page: 773
  year: 2015
  ident: ref23
  article-title: Essential gene disruptions reveal complex relationships between phenotypic robustness, pleiotropy, and fitness
  publication-title: Mol Syst Biol
  doi: 10.15252/msb.20145264
– volume: 23
  start-page: 1870
  year: 2009
  ident: ref60
  article-title: The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells
  publication-title: Genes Dev
  doi: 10.1101/gad.1823109
– volume: 22
  start-page: 1356
  year: 2013
  ident: ref25
  article-title: Multiple capacitors for natural genetic variation in Drosophila melanogaster
  publication-title: Mol Ecol
  doi: 10.1111/mec.12091
– volume: 83
  start-page: 599
  year: 1995
  ident: ref47
  article-title: pop-1 encodes an HMG box protein required for the specification of a mesoderm precursor in early C. elegans embryos
  publication-title: Cell
  doi: 10.1016/0092-8674(95)90100-0
– volume: 298
  start-page: 840
  year: 2002
  ident: ref69
  article-title: Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop
  publication-title: Science
  doi: 10.1126/science.1074560
– volume: 66
  start-page: 2878
  year: 2012
  ident: ref26
  article-title: Deficiency screening for genomic regions with effects on environmental sensitivity of the sensory bristles of Drosophila melanogaster
  publication-title: Evolution
  doi: 10.1111/j.1558-5646.2012.01636.x
SSID ssj0022928
Score 2.3617277
Snippet Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits...
SourceID plos
doaj
pubmedcentral
proquest
gale
pubmed
crossref
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
StartPage e2002429
SubjectTerms Animals
Biochemistry
Biology and Life Sciences
Caenorhabditis elegans
Caenorhabditis elegans - genetics
Caenorhabditis elegans - growth & development
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Cell Count
Cell Differentiation
Cell Division
Cell Lineage
Cell number
Cells, Cultured
CRISPR
Data collection
Developmental biology
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Epidermal Cells
Epidermis
Epidermis - metabolism
Feasibility studies
Gene expression
Gene Expression Regulation
Genetic variability
Genetics
Genomes
Helix-loop-helix proteins
Helix-loop-helix proteins (basic)
Life sciences
Molecular physics
Mutagenesis
Mutants
Mutation
Nematodes
Physiological aspects
Research and Analysis Methods
Screens
Signal transduction
Signaling
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Stochastic Processes
Stochasticity
Transcription factors
Transcription Factors - genetics
Transcription Factors - metabolism
University colleges
Variability
Wnt protein
Wnt Signaling Pathway
SummonAdditionalLinks – databaseName: DOAJ Open Access Full Text
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3da9wwDDfjYLCXse9e1w1vDPaUNnYcO37syko3WAfrOvoWbMduD3rJcc499L-flORCMzq6h72e5ISTZEuKpZ8I-WB5kJAei6SyWiSCBZ1YqVVSsSC4kT4NHBucv53Kk3Px9SK_uDXqC2vCenjgXnAHkitwaoWzQlWC47VSxSUvjLGuCKns2nzB522TqSHV4rqbqopQM7CdVTY0zWWKHQw62l_ZRdf8Bz5KT5xSh90_ntCz1XUT7wo__6yivOWWjp-Qx0M8SQ_7__GUPPD1M_KwnzB585zEs7ZxVwbBmCm8IVJTV_TSLGraBBpvlkscqOUoNmXhZ7NIgQIhIT3apziQAvwY9ThDFs2BrvwaHJSNdN3YTWzxkOwe0_olxQsA2o8XeUHOjz__PDpJhjkLiVOStYllzFdB4DRcA6LzRgUthAGV6YABjFKGp8Fzz3MnDLdB85BVsJtNkbncmuwlmdVN7XcIhWWYbDvrci4c84XRyrIqzcAmHHNqTrKtoEs3gJDjLIzrsrtZU5CM9HIrUT3loJ45ScZVqx6E4x7-T6jDkRchtLsfwLDKwbDK-wxrTt6jBZQIklFjFc6l2cRYfvn-qzzMGeLcpVr9jens9F-YfkyYPg5MoQGJODO0R4BcEaFrwrk34QQDcBPyDprsVjCxxKo4hGnLJazcmvHd5HcjGR-K5Xe1bzbIIyFuhzgGRPuqt_pRuFxjmSpS1GQ_TKQ_pdSLqw7IPEeU7KLY_R_qek0ecYy48Iu_3COzdr3xbyBebO3b7mj4DTABZrQ
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: Scholars Portal Journals: Open Access
  dbid: M48
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3db9MwELdGERIviO8VBjIIiadUjePYyQNCY2IaSBsSo2hvke3YXaU2KXUq0f-eu3yJoA547Z2d6nyXO8fn34-QN5o5AdtjHuQ65QEPXRpokcogDx1nStipY3jB-fxCnM3456v46oB0nK2tAf3erR3ySc02y8nPH7v3EPDvatYGGXaDJmu9qK_zQdZJb5HbkJskhuo5788VGEtrtlWEoIEwl1F7me6mWQbJqsb079_co_Wy9PvK0j-7K39LV6f3yb22zqTHjWM8IAe2eEjuNMyTu0fEX1aluVYI0kzhCZ6qIqdztSho6ajfrVZItGUoXtbCz2meggRKRXoyoUhUAfmNWuSWRTeha7uBxKU93ZR66yt8edbTVHZF8WCANrQjj8ns9OO3k7Og5V8IjBRhFegwtLnjyJKrwHRWSZdyrmApU4eFjZSKTZ1llsWGK6ZdylyUQ5SrJDKxVtETMirKwh4SCsNwE260iRk3oU1UKnWYTyPwFRMaOSZRZ-jMtODkyJGxzOoTNwmblMZuGS5P1i7PmAT9qHUDzvEP_Q-4hr0uQmvXP5SbedZGaiaYhCoqMZrLnDM8x8yZYIlS2iRuKpIxeY0ekCF4RoHdOXO19T779OV7dhyHiH83TeVNSpcX_6P0daD0tlVyJVjEqPbaBNgVkbsGmkcDTXAAMxAfost2hvEZdsshfFssYGTnxvvFr3oxTopteYUtt6gjoJ6H-gZM-7Tx-t64LMX2VZTIQTwMrD-UFIvrGuA8RvTsJHn297_1nNxlWGPhN35xREbVZmtfQIVY6Zd10P8CeD9k7g
  priority: 102
  providerName: Scholars Portal
Title Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number
URI https://www.ncbi.nlm.nih.gov/pubmed/29108019
https://www.proquest.com/docview/1989018056
https://www.proquest.com/docview/1961634719
https://pubmed.ncbi.nlm.nih.gov/PMC5690688
https://doaj.org/article/6277508cb47d427395d2628aabc8f068
http://dx.doi.org/10.1371/journal.pbio.2002429
Volume 15
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3db9MwELegExIviO8VRmUQEk_ZGsexkye0TZsGaAU2hvoW2Y7dVVqT0KQP---5S9yOoPHxkofeOY3Od_bZPv9-hLzVzAlYHvMg1ykPeOjSQItUBnnoOFPCjh3DC86nE3FywT9O46nfcKt9WeV6TGwH6rw0uEe-h7U9CDYVi_fVjwBZo_B01VNo3CVbCF2GJV1yerPgYmnLrYqAMxDUMvJX5yIZ7vme2q30vL0CCDNV2puaWgT_zTg9qK7K-rYk9Pdayl8mp-OH5IHPKul-5waPyB1bPCb3Op7J6yekPm9Kc6kQkpnCP9RUFTmdqXlBS0fr68UCabUMxatZuHlWU5BAYkgPdynSUsBsRi0yyaJT0MouYZrSNV2WelU3OFS2r2nsguIxAO1IRp6Si-Ojb4cngWdbCIwUYRPoMLS548iJq8B0VkmXcq6g41KHaYyUio2dZZbFhiumXcpclENMqyQysVbRMzIoysJuEwrNcMlttIkZN6FNVCp1mI8j8AwTGjkk0drQmfFQ5MiIcZW152sSliSd3TLsnsx3z5AEm1ZVB8XxD_0D7MONLgJptz-Uy1nm4zITTELOlBjNZc4ZnlrmTLBEKW0SNxbJkLxBD8gQKqPAWpyZWtV19uHz92w_DhHtbpzKPymdT_5H6ayn9M4ruRIsYpS_JAF2RZyunuZOTxMcwPTE2-iya8PU2U38QMu1G98ufr0R40uxCK-w5Qp1BGTvkM2AaZ93Xr8xLkuxWBUlshcPPev3JcX8soUzjxErO0le_P2zXpL7DDMq3NEXO2TQLFf2FeSDjR61QT8iWwdHky9no3ZXBZ6fvibwPOXJTzuvY48
linkProvider ProQuest
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9NAEF6VVAguiHcDBRYE4uQ2Xq-99gGhtrRKaBtQX-rN7K5300iNHeJEKH-K38iMX2BUHpdeM7Mba3Y8D-_MfIS8VswGkB5zJ1ERd7hrI0cFkXAS13ImA9OzDBucD4dB_5R_PPfPV8j3uhcGyyprm1gY6iTT-I18E2t7cNiUH7yffnUQNQpvV2sIjVIt9s3yG6Rs-bvBBzjfN4zt7Z7s9J0KVcDRkLLPHeW6JrEcsV8lODAjhY04l_CAkUV3LYRkPWuYYb7mkikbMesloLsy9LSvpAf73iCr3INUpkNWt3eHn4-aFI9FBZorjrgBMyK8qlnPE-5mpRsbUzUumg7BN0YtZ1hgBjSeoTO9zPKrwt7fqzd_cYd7d8mdKo6lW6Xi3SMrJr1PbpbIlssHJD-eZ_pC4hBoCv-QU5kmdCTHKc0szZeTCQJ5aYrNYPi5LqdAgVCU7mxQBMIA_0kNYteiGtKpmYFjVDmdZWqRz9E4F9vMzYTixQMtYU0ektNrOYlHpJNmqVkjFJZhkq-V9hnXrgllJJSb9DzQRe1q0SVeLehYV8PPEYPjMi5u9AQkQaXcYjyeuDqeLnGaVdNy-Mc_-LfxDBteHN1d_JDNRnFlCeKACYjSQq24SDjDe9KEBSyUUunQ9oKwS16hBsQ4nCPF6p-RXOR5PPh0Fm_5Ls7X60XiT0zHw_9hOmoxva2YbAYS0bJqywC54mSwFud6ixMUQLfIa6iytWDy-OcbCytrNb6a_LIh46ZY9peabIE8AeQLED-BaB-XWt8Il0VYHosU0XofWtJvU9LxRTFA3cfp3GH45O-P9YLc6p8cHsQHg-H-U3KbYTyH9wnBOunMZwvzDKLRuXpemQBKvly31fkBYEedMg
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV3db9MwELdGEYiXie91DDAIxFPWxnHi5AGhsVGtDApiDPUt2I7dVVqT0qRC_df467jLR0fQ-HjZa--cRufzfcR39yPkmWI2gPSYO4mKuMNdGzkqiISTuJYzGZi-Zdjg_H4UHJ7wt2N_vEF-NL0wWFbZ2MTSUCeZxm_kPaztwWFTftCzdVnEx4PBq_k3BxGk8Ka1gdOoVOTIrL5D-pa_HB7AXj9nbPDm8_6hUyMMOBrS98JRrmsSyxEHVoIzM1LYiHMJLxtZdN1CSNa3hhnmay6ZshGzXgJ6LENP-0p68Nwr5KrwfBfPmBifJ3ssKnFdcdgNGBTh1W17nnB7tZbsztW0bD8ELxm13GKJHrD2EZ35WZZfFAD_Xsf5i2Mc3CSbdURL9yoVvEU2THqbXKswLld3SH5cZPpU4jhoCv-QU5kmdCKnKc0szVezGUJ6aYptYfjhLqdAgaCU7u9ShMQAT0oNotiiQtK5WYCLVDldZGqZF2imy8cUZkbxCoJWACd3ycml7MM90kmz1GwRCssw3ddK-4xr14QyEspN-h5opXa16BKvEXSs6zHoiMZxFpd3ewLSoUpuMW5PXG9PlzjrVfNqDMg_-F_jHq55cYh3-UO2mMS1TYgDJiBeC7XiIuEMb0wTFrBQSqVD2w_CLnmKGhDjmI4UFX4il3keDz98ifd8Fyft9SPxJ6bj0f8wfWoxvaiZbAYS0bJu0AC54oywFudOixMUQLfIW6iyjWDy-PzswspGjS8mP1mT8aFYAJiabIk8AWQOEEmBaO9XWr8WLouwUBYponUeWtJvU9LpaTlK3cc53WG4_ffXekyug62J3w1HRw_IDYaBHV4sBDukUyyW5iGEpYV6VJ5_Sr5etsH5Cd0LoAI
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Stochastic+loss+and+gain+of+symmetric+divisions+in+the+C.+elegans+epidermis+perturbs+robustness+of+stem+cell+number&rft.jtitle=PLoS+biology&rft.au=Katsanos%2C+Dimitris&rft.au=Koneru%2C+Sneha+L&rft.au=Lamia+Mestek+Boukhibar&rft.au=Gritti%2C+Nicola&rft.date=2017-11-06&rft.pub=Public+Library+of+Science&rft.issn=1544-9173&rft.eissn=1545-7885&rft.volume=15&rft.issue=11&rft_id=info:doi/10.1371%2Fjournal.pbio.2002429&rft.externalDBID=HAS_PDF_LINK
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1545-7885&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1545-7885&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1545-7885&client=summon