Pax6 mutant cerebral organoids partially recapitulate phenotypes of Pax6 mutant mouse strains

Cerebral organoids show great promise as tools to unravel the complex mechanisms by which the mammalian brain develops during embryogenesis. We generated mouse cerebral organoids harbouring constitutive or conditional mutations in Pax6, which encodes a transcription factor with multiple important ro...

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Published inPloS one Vol. 17; no. 11; p. e0278147
Main Authors Ferdaos, Nurfarhana, Lowell, Sally, Mason, John O
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 28.11.2022
Public Library of Science (PLoS)
Subjects
Analysis
Animal models
Animals
Biology and Life Sciences
Brain
Cell cycle
Cell differentiation
Embryogenesis
Embryonic development
Embryonic growth stage
Embryos
Gene mutations
Genetic aspects
Health aspects
Mammals
Mice
Mice, Mutant Strains
Mitosis
Mutants
Mutation
Neural stem cells
Neurons
Organoids
Pax6 protein
PAX6 Transcription Factor - genetics
Phenotype
Phenotypes
Physiological aspects
Progenitor cells
Research and Analysis Methods
Rodents
Transcription factors
United Kingdom
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Summary:Cerebral organoids show great promise as tools to unravel the complex mechanisms by which the mammalian brain develops during embryogenesis. We generated mouse cerebral organoids harbouring constitutive or conditional mutations in Pax6, which encodes a transcription factor with multiple important roles in brain development. By comparing the phenotypes of mutant organoids with the well-described phenotypes of Pax6 mutant mouse embryos, we evaluated the extent to which cerebral organoids reproduce phenotypes previously described in vivo. Organoids lacking Pax6 showed multiple phenotypes associated with its activity in mice, including precocious neural differentiation, altered cell cycle and an increase in abventricular mitoses. Neural progenitors in both Pax6 mutant and wild type control organoids cycled more slowly than their in vivo counterparts, but nonetheless we were able to identify clear changes to cell cycle attributable to the absence of Pax6. Our findings support the value of cerebral organoids as tools to explore mechanisms of brain development, complementing the use of mouse models.
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Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0278147