Ptf1a determines horizontal and amacrine cell fates during mouse retinal development

Yoshio Fujitani, Shuko Fujitani, Huijun Luo, Feng Qiu, Jared Burlison, Qiaoming Long, Yoshiya Kawaguchi, Helena Edlund, Raymond J. MacDonald, Takashi Furukawa, Takashi Fujikado, Mark A. Magnuson, Mengqing Xiang, Christopher V E Wright

Research output: Contribution to journalArticle

155 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4439-4450
Number of pages12
JournalDevelopment
Volume133
Issue number22
DOIs
StatePublished - Nov 1 2006

Keywords

  • Amacrine cell
  • Basic helix-loop-helix
  • Cell specification
  • Foxn4
  • Ganglion cell
  • Horizontal cell
  • Lineage tracing
  • Progenitor
  • Ptf1a
  • Retinal development

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Fujitani, Y., Fujitani, S., Luo, H., Qiu, F., Burlison, J., Long, Q., Kawaguchi, Y., Edlund, H., MacDonald, R. J., Furukawa, T., Fujikado, T., Magnuson, M. A., Xiang, M., & Wright, C. V. E. (2006). Ptf1a determines horizontal and amacrine cell fates during mouse retinal development. Development, 133(22), 4439-4450. https://doi.org/10.1242/dev.02598