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The Journal of Neuroscience, January 7, 2004, 24(1):229-237; doi:10.1523/JNEUROSCI.2980-03.2004

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Development/Plasticity/Repair
Persistent Progenitors at the Retinal Margin of ptc+/- Mice

Ala Moshiri and Thomas A. Reh

Neurobiology and Behavior Program, Department of Biological Structure, University of Washington, School of Medicine, Seattle, Washington 98195

The hedgehog signaling pathway is a key regulator of neural development, affecting both proliferation and differentiation of neural progenitors. Sonic hedgehog (Shh) is a mitogenic factor for retinal progenitors in vitro. To determine whether this signaling system is important in vivo for regulating retinal progenitor proliferation, we analyzed mice with a single functional allele of the Shh receptor patched (ptc). We found that ptc+/- mice had increased numbers of neural progenitors at every stage of retinal development that we examined. In addition, these mice had persistent progenitors at the retinal margin for up to 3 months of age, reminiscent of the ciliary marginal zone of lower vertebrates. To test whether the progenitors at the retinal margin of ptc+/- mice could be induced to regenerate retinal neurons in response to damage, we bred ptc+/- mice onto a retinal degeneration background (pro23his rhodopsin transgenic) and labeled newly generated cells with combined immunohistochemistry for bromodeoxyuridine and retinal neuron and photoreceptor-specific markers. We found newly generated neurons and photoreceptors at the retinal margin in ptc+/-;pro23his mice. We propose that the Shh pathway may act as a regulator of both prenatal and postnatal retinal growth.

Key words: development; regeneration; retina; neurogenesis; progenitor; stem cell

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Received June 17, 2003; revised October 28, 2003; accepted November 6, 2003.

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