DSCAM promotes self-avoidance in the developing mouse retina by masking the functions of cadherin superfamily members

During neural development, self-avoidance ensures that a neuron’s processes arborize to evenly fill a particular spatial domain. At the individual cell level, self-avoidance is promoted by genes encoding cell-surface molecules capable of generating thousands of diverse isoforms, such as Dscam1 (Down...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 115; no. 43; pp. E10216 - E10224
Main Authors Garrett, Andrew M., Khalil, Andre, Walton, David O., Burgess, Robert W.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 23.10.2018
SeriesPNAS Plus
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:During neural development, self-avoidance ensures that a neuron’s processes arborize to evenly fill a particular spatial domain. At the individual cell level, self-avoidance is promoted by genes encoding cell-surface molecules capable of generating thousands of diverse isoforms, such as Dscam1 (Down syndrome cell adhesion molecule 1) in Drosophila. Isoform choice differs between neighboring cells, allowing neurons to distinguish “self” from “nonself”. In the mouse retina, Dscam promotes self-avoidance at the level of cell types, but without extreme isoform diversity. Therefore, we hypothesize that DSCAM is a general self-avoidance cue that “masks” other cell type-specific adhesion systems to prevent overly exuberant adhesion. Here, we provide in vivo and in vitro evidence that DSCAM masks the functions of members of the cadherin superfamily, supporting this hypothesis. Thus, unlike the isoform-rich molecules tasked with self-avoidance at the individual cell level, here the diversity resides on the adhesive side, positioning DSCAM as a generalized modulator of cell adhesion during neural development.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Author contributions: A.M.G. and R.W.B. designed research; A.M.G. performed research; A.K. and D.O.W. contributed new reagents/analytic tools; A.M.G. and A.K. analyzed data; and A.M.G. and R.W.B. wrote the paper.
Edited by S. Lawrence Zipursky, University of California, Los Angeles, CA, and approved September 12, 2018 (received for review June 1, 2018)
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1809430115