Integral bHLH factor regulation of cell cycle exit and RGC differentiation

Kate A. Maurer, Angelica Kowalchuk, Farnaz Shoja-Taheri, Nadean L Brown

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: In the developing mouse embryo, the bHLH transcription factor Neurog2 is transiently expressed by retinal progenitor cells and required for the initial wave of neurogenesis. Remarkably, another bHLH factor, Ascl1, normally not present in the embryonic Neurog2 retinal lineage, can rescue the temporal phenotypes of Neurog2 mutants. Results: Here we show that Neurog2 simultaneously promotes terminal cell cycle exit and retinal ganglion cell differentiation, using mitotic window labeling and integrating these results with retinal marker quantifications. We also analyzed the transcriptomes of E12.5 GFP-expressing cells from Neurog2GFP/+, Neurog2GFP/GFP, and Neurog2Ascl1KI/GFP eyes, and validated the most significantly affected genes using qPCR assays. Conclusions: Our data support the hypothesis that Neurog2 acts at the top of a retinal bHLH transcription factor hierarchy. The combined expression levels of these downstream factors are sufficiently induced by ectopic Ascl1 to restore RGC genesis, highlighting the robustness of this gene network during retinal ganglion cell neurogenesis. Developmental Dynamics 247:965-975, 2018.

Original languageEnglish (US)
Pages (from-to)965-975
Number of pages11
JournalDevelopmental Dynamics
Volume247
Issue number8
DOIs
StatePublished - Aug 1 2018

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Basic Helix-Loop-Helix Transcription Factors
Retinal Ganglion Cells
Neurogenesis
Cell Cycle
Gene Regulatory Networks
Transcriptome
Cell Differentiation
Stem Cells
Embryonic Structures
Phenotype
Genes

Keywords

  • Ascl
  • Atoh7
  • bHLH factor
  • Neurog2
  • neurogenesis
  • retinal ganglion cell

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Integral bHLH factor regulation of cell cycle exit and RGC differentiation. / Maurer, Kate A.; Kowalchuk, Angelica; Shoja-Taheri, Farnaz; Brown, Nadean L.

In: Developmental Dynamics, Vol. 247, No. 8, 01.08.2018, p. 965-975.

Research output: Contribution to journalArticle

Maurer, Kate A. ; Kowalchuk, Angelica ; Shoja-Taheri, Farnaz ; Brown, Nadean L. / Integral bHLH factor regulation of cell cycle exit and RGC differentiation. In: Developmental Dynamics. 2018 ; Vol. 247, No. 8. pp. 965-975.
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