Pax6 is essential for the generation of late-born retinal neurons and for inhibition of photoreceptor-fate during late stages of retinogenesis

Liv Aleen Remez, Akishi Onishi, Yotam Menuchin-Lasowski, Assaf Biran, Seth Blackshaw, Karl J. Wahlin, Donlad J. Zack, Ruth Ashery-Padan

Research output: Contribution to journalArticlepeer-review

Abstract

In the developing retina, as in other regions of the CNS, neural progenitors give rise to individual cell types during discrete temporal windows. Pax6 is expressed in retinal progenitor cells (RPCs) throughout the course of retinogenesis, and has been shown to be required during early retinogenesis for generation of most early-born cell types. In this study, we examined the function of Pax6 in postnatal mouse retinal development. We found that Pax6 is essential for the generation of late-born interneurons, while inhibiting photoreceptor differentiation. Generation of bipolar interneurons requires Pax6 expression in RPCs, while Pax6 is required for the generation of glycinergic, but not for GABAergic or non-GABAergic-non-glycinergic (nGnG) amacrine cell subtypes. In contrast, overexpression of either full-length Pax6 or its 5a isoform in RPCs induces formation of cells with nGnG amacrine features, and suppresses generation of other inner retinal cell types. Moreover, overexpression of both Pax6 variants prevents photoreceptor differentiation, most likely by inhibiting Crx expression. Taken together, these data show that Pax6 acts in RPCs to control differentiation of multiple late-born neuronal cell types.

Original languageEnglish (US)
Pages (from-to)140-150
Number of pages11
JournalDevelopmental biology
Volume432
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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