Math5 is required for both early retinal neuron differentiation and cell cycle progression

Tien T. Le, Emily Wroblewski, Sima Patel, Amy N. Riesenberg, Nadean L Brown

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

CNS progenitors choose a fate, exit mitosis and differentiate. Basic helix-loop-helix (bHLH) transcription factors are key regulators of neurogenesis, but their molecular mechanisms remain unclear. In the mouse retina, removal of the bHLH factor Math5 (Atoh7) causes the loss of retinal ganglion cells (RGCs) and appearance of excess cone photoreceptors. Here, we show a simultaneous requirement for Math5 in retinal neuron formation and cell cycle progression. At embryonic day E11.5, Math5-/- cells are unable to assume the earliest fates, particularly that of an RGC, and instead adopt the last fate as Müller glia. Concurrently, the loss of Math5 causes mitotically active retinal progenitors to undergo aberrant cell cycles. The drastic fate shift of Math5-/- cells correlates with age-specific alterations in p27/Kip1 expression and an inability to become fully postmitotic. Finally, Math5 normally suppresses NeuroD1 within Math5-expressing cells and inhibits Ngn2 expression and cone photoreceptor genesis within separate cell populations. Thus, Math5 orchestrates neurogenesis in multiple ways, regulating both intrinsic and extrinsic processes.

Original languageEnglish (US)
Pages (from-to)764-778
Number of pages15
JournalDevelopmental Biology
Volume295
Issue number2
DOIs
StatePublished - Jul 15 2006
Externally publishedYes

Keywords

  • bHLH
  • Cell cycle progression
  • Math5
  • Mouse
  • NeuroD1
  • Neurogenesis
  • Ngn2
  • Retina
  • RGC

ASJC Scopus subject areas

  • Developmental Biology

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