Ptf1a determines horizontal and amacrine cell fates during mouse retinal development

Development. 2006 Nov;133(22):4439-50. doi: 10.1242/dev.02598.

Abstract

The vertebrate neural retina comprises six classes of neurons and one class of glial cells, all derived from a population of multipotent progenitors. There is little information on the molecular mechanisms governing the specification of cell type identity from multipotent progenitors in the developing retina. We report that Ptf1a, a basic-helix-loop-helix (bHLH) transcription factor, is transiently expressed by post-mitotic precursors in the developing mouse retina. Recombination-based lineage tracing analysis in vivo revealed that Ptf1a expression marks retinal precursors with competence to exclusively produce horizontal and amacrine neurons. Inactivation of Ptf1a leads to a fate-switch in these precursors that causes them to adopt a ganglion cell fate. This mis-specification of neurons results in a complete loss of horizontal cells, a profound decrease of amacrine cells and an increase in ganglion cells. Furthermore, we identify Ptf1a as a primary downstream target for Foxn4, a forkhead transcription factor involved in the genesis of horizontal and amacrine neurons. These data, together with the previous findings on Foxn4, provide a model in which the Foxn4-Ptf1a pathway plays a central role in directing the differentiation of retinal progenitors towards horizontal and amacrine cell fates.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amacrine Cells / embryology*
  • Amacrine Cells / metabolism
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • DNA Primers
  • Eye Proteins / metabolism
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental*
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Retinal Horizontal Cells / embryology*
  • Retinal Horizontal Cells / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology

Substances

  • DNA Primers
  • Eye Proteins
  • Forkhead Transcription Factors
  • Foxn4 protein, mouse
  • Transcription Factors
  • transcription factor PTF1