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Chunqiao Liu, Hirva Bakeri, Anand Swaroop; Regulation Of Retinal Neurogenesis By Frizzled Receptors. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6006.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the role of Wnt-Frizzled signaling in retinal development.
Fz5 and Fz8 compound mutant mice were generated. Retinal neurogenesis was analyzed by immunohistochemistry for early born neurons. BrdU pulse was used to study cell cycle exit rate. Frizzleds’ function was investigated with acute retinal explants, in vitro. Phalloidin was used to stain neuroblast F-actin, laminin was used to study ECM deposition. Hes1 expression was examined by in situ hybridization to monitor changes in Shh and or Notch signaling pathway.
Embryos lacking both Fz5 and Fz8 die in early development. A majority of triallelic Fz5-/-;Fz8+/- mutants that survive until birth develop severe retinal coloboma and microphthalmia with full penetrance. Ganglion and amacrine cell populations are disproportionally large at E17.5. Increased cell cycle exit of retinal progenitors was detected at E13. Neuroblast organization and apical basal polarity are perturbed. Hes1, a common target of Shh and Notch signaling, is downregulated. In vitro blocking of Frizzled receptors leads to randomized divisions of progenitors along the retinal neuroblast layer.
Fz8 and Fz5 signaling in a dose-dependent manner controls retinal progenitor expansion.
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