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First published online 27 April 2005
doi: 10.1242/dev.01831

Development 132, 2573-2585 (2005)
Published by The Company of Biologists 2005
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Staggered cell-intrinsic timing of ath5 expression underlies the wave of ganglion cell neurogenesis in the zebrafish retina

Jeremy N. Kay1,*, Brian A. Link2 and Herwig Baier1

1 Department of Physiology and Programs in Neuroscience, Genetics, and Developmental Biology, University of California, 1550 Fourth Street, San Francisco, CA 94158, USA
2 Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226-0509, USA

* Author for correspondence (e-mail: jnk{at}phy.ucsf.edu)

Accepted 22 March 2005

In the developing nervous system, progenitor cells must decide when to withdraw from the cell cycle and commence differentiation. There is considerable debate whether cell-extrinsic or cell-intrinsic factors are most important for triggering this switch. In the vertebrate retina, initiation of neurogenesis has recently been explained by a `sequential-induction' model – signals from newly differentiated neurons are thought to trigger neurogenesis in adjacent progenitors, creating a wave of neurogenesis that spreads across the retina in a stereotypical manner. We show here, however, that the wave of neurogenesis in the zebrafish retina can emerge through the independent action of progenitor cells – progenitors in different parts of the retina appear pre-specified to initiate neurogenesis at different times. We provide evidence that midline Sonic hedgehog signals, acting before the onset of neurogenesis, are part of the mechanism that sets the neurogenic timer in these cells. Our results highlight the importance of intrinsic factors for triggering neurogenesis, but they also suggest that early signals can modulate these intrinsic factors to influence the timing of neurogenesis many cell cycles later, thereby potentially coordinating axial patterning with control of neuron number and cell fate.

Key words: Zebrafish, ath5 (atoh7), Proneural genes, Atonal, Sonic Hedgehog


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