Zac1 promotes a Müller glial cell fate and interferes with retinal ganglion cell differentiation in Xenopus retina

Dev Dyn. 2007 Jan;236(1):192-202. doi: 10.1002/dvdy.21002.

Abstract

The timing of cell cycle exit is tightly linked to cell fate specification in the developing retina. Accordingly, several tumor suppressor genes, which are key regulators of cell cycle exit in cancer cells, play critical roles in retinogenesis. Here we investigated the role of Zac1, a tumor suppressor gene encoding a zinc finger transcription factor, in retinal development. Strikingly, in gain-of-function assays in Xenopus, mouse Zac1 promotes proliferation and apoptosis at an intermediate stage of retinogenesis. Zac1 also influences cell fate decisions, preferentially promoting the differentiation of tumor-like clusters of abnormal neuronal cells in the ganglion cell layer, as well as inducing the formation of supernumerary Müller glial cells at the expense of other cell types. Thus Zac1 has the capacity to influence cell cycle exit, and cell fate specification and differentiation decisions by retinal progenitors, suggesting that further functional studies will uncover new insights into how retinogenesis is regulated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Cell Differentiation
  • Cell Lineage
  • Genes, Tumor Suppressor / physiology*
  • Immunohistochemistry
  • Mice
  • Morphogenesis
  • Neuroglia / cytology*
  • Retina / embryology*
  • Retina / physiology
  • Retinal Ganglion Cells / cytology*
  • Retinal Ganglion Cells / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Xenopus laevis
  • Zinc Fingers

Substances

  • Cell Cycle Proteins
  • Plagl1 protein, mouse
  • Transcription Factors