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First published online October 30, 2006
doi: 10.1242/10.1242/dev.02598

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Ptf1a determines horizontal and amacrine cell fates during mouse retinal development

Yoshio Fujitani^1,*,,, Shuko Fujitani^1,2,*, Huijun Luo³, Feng Qiu³, Jared Burlison⁴, Qiaoming Long⁴, Yoshiya Kawaguchi⁵, Helena Edlund⁶, Raymond J. MacDonald⁷, Takahisa Furukawa⁸, Takashi Fujikado², Mark A. Magnuson⁴, Mengqing Xiang³ and Christopher V. E. Wright^1,

¹ Vanderbilt University Program in Developmental Biology and Department of Cell and Developmental Biology, Vanderbilt University Medical School, Nashville, TN 37232-8240, USA.
² Department of Visual Science, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
³ Center for Advanced Biotechnology and Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, USA.
⁴ Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0615, USA.
⁵ Department of Surgery and Surgical Basic Science, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
⁶ Umeå Center for Molecular Medicine, University of Umeå, SE-901 87 Umeå, Sweden.
⁷ Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
⁸ Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.

Authors for correspondence (e-mail: yoshio-f{at}osb.att.ne.jp; christopher.wright{at}vanderbilt.edu)

Accepted 30 August 2006

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.

Key words: Retinal development, Basic helix-loop-helix, Amacrine cell, Horizontal cell, Ganglion cell, Lineage tracing, Ptf1a, Foxn4, Progenitor, Cell specification

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