Persistent progenitors at the retinal margin of ptc+/- mice.
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.
Moshiri
Ala
A
Neurobiology and Behavior Program, Department of Biological Structure, University of Washington, School of Medicine, Seattle, Washington 98195, USA.
Reh
Thomas A
TA
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D012038:Regeneration; D012160:Retina / Q000166:cytology* / Q000254:growth & development* / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface