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First published online 12 November 2008
doi: 10.1242/dev.028308

Development 135, 4037-4047 (2008)
Published by The Company of Biologists 2008
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Dual requirement for Pax6 in retinal progenitor cells

Varda Oron-Karni1,*, Chen Farhy1,*, Michael Elgart1, Till Marquardt2, Lena Remizova1, Orly Yaron1, Qing Xie3, Ales Cvekl3 and Ruth Ashery-Padan1,{dagger}

1 Sackler Faculty of Medicine, Human Molecular Genetics and Biochemistry, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel.
2 European Neuroscience Institute, Developmental Neurobiology Laboratory, University of Göttingen Medical School/Max Planck Society, Grisebachstrasse 5, 37077 Göttingen, Germany.
3 Albert Einstein College of Medicine, Departments of Ophthalmology and Visual Sciences and Genetics, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

{dagger} Author for correspondence (e-mail: ruthash{at}post.tau.ac.il)

Accepted 8 October 2008

Throughout the developing central nervous system, pre-patterning of the ventricular zone into discrete neural progenitor domains is one of the predominant strategies used to produce neuronal diversity in a spatially coordinated manner. In the retina, neurogenesis proceeds in an intricate chronological and spatial sequence, yet it remains unclear whether retinal progenitor cells (RPCs) display intrinsic heterogeneity at any given time point. Here, we performed a detailed study of RPC fate upon temporally and spatially confined inactivation of Pax6. Timed genetic removal of Pax6 appeared to unmask a cryptic divergence of RPCs into qualitatively divergent progenitor pools. In the more peripheral RPCs under normal circumstances, Pax6 seemed to prevent premature activation of a photoreceptor-differentiation pathway by suppressing expression of the transcription factor Crx. More centrally, Pax6 contributed to the execution of the comprehensive potential of RPCs: Pax6 ablation resulted in the exclusive generation of amacrine interneurons. Together, these data suggest an intricate dual role for Pax6 in retinal neurogenesis, while pointing to the cryptic divergence of RPCs into distinct progenitor pools.

Key words: Pax6, Retinal progenitor cells, Retinogenesis, Crx, Cre/loxP


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