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D. Wall, Y. Wang, V. Wallace; Interaction Between the Shh and Notch Signaling Pathways in Retinal Development . Invest. Ophthalmol. Vis. Sci. 2005;46(13):586.
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Purpose: Proper morphological neural development is achieved through a precise mechanism of time–dependent cellular differentiation. As embryogenesis ensues, precursor cells will either replicate or differentiate into their destined cell type dependent on the activity of negative or positive regulators of neuronal differentiation. This ensures that the appropriate numbers of differentiated cell types constitute the developed neural tissue. Sonic hedgehog (Shh) is a secreted protein important for proper organization and patterning of neural tissues including the retina. Shh derived from retinal ganglion cells is required for controlling proliferation and inhibiting differentiation of retinal precursor cells thereby ensuring cell diversification of the retinal tissue. The Notch signaling pathway also inhibits cellular differentiation of developing neural tissue via regulation of its effectors Hes1 and Hes5. Mice with a conditional ablation of Shh show a down–regulation of Hes1 expression indicating a possible convergence of the Shh and Notch signaling pathways. The purpose of this study was to determine whether a genetic interaction exists between the Shh and Notch signaling pathways in the development of the neural retina. Methods: A mouse model harboring a conditional inactivation of Shh (Pax6–Cre;Shh–/c) in the peripheral retina was crossed with mice heterozygous for Hes1. Histology, immunohistochemistry and in situ hybridization was used to study retinal morphology, and to detect changes in markers for cellular proliferation, differentiation, and cell type specification. Results: The retinas of mice with a conditional ablation of Pax6–Cre;Shh–/c;Hes+/– mice exhibit marked alterations in retinal development, including an increase in retinal ganglion cell development, compared with Pax6–Cre;Shh–/c littermates. Conclusions: The Sonic hedgehog pathway may mediate its effects on retinal precursor cell differentiation in part through the activity of Hes1.
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