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Kathryn B. Moore, Mary A. Logan, Issam Al Diri, Monica L. Vetter; The Proneural Target Gene Sbt1 Regulates Neurogenesis By Governing Proliferation In The Xenopus Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6012.
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© ARVO (1962-2015); The Authors (2016-present)
Proneural basic helix-loop helix (bHLH) transcription factors are key regulators of retinal neurogenesis, activating the expression of target genes that execute a program of neuronal differentiation within progenitors. Our study focuses on understanding this differentiation program in Xenopus retinal progenitors by examining the function of bHLH target genes.
We performed a screen for proneural target genes, identifying a novel gene called sbt1 (shared bHLH target 1). sbt1 encodes a novel protein with no conserved functional motifs that is conserved across vertebrate species. We used in situ hybridization and gain and loss of function approaches to elucidate the spatial and temporal expression of sbt1 and to gain insight into its function during retinal development.
In situ hybridization analysis showed that sbt1 is transiently expressed in late proliferating and early differentiating cells in the Xenopus retina and is localized both at the membrane and in the nucleus. Overexpression of either mouse or Xenopus sbt1 in progenitors promoted differentiation of early born retinal neurons, and also enhanced the ability of the bHLH factor Ath5 to promote neurogenesis. Conversely, inhibition of SBT1 translation in Xenopus retinal progenitors by injection of antisense morpholino into cleavage-stage blastomeres prevented/delayed retinal neuron differentiation, resulting in an increase in Müller glia and progenitors. Loss of function of sbt1 in retinal progenitors blocked the expression of markers for differentiated retinal neurons suggesting that it is required for full proneural function. In addition, overexpression of sbt1 caused a reduction in mitotic cells in the optic vesicle as measured by phospho-histone H3 staining. We performed a yeast 2-hybrid screen for SBT1 interactors and have isolated several potential protein partners, including proteins involved in cell cycle regulation.
Based on these results, we propose that sbt1 is expressed in retinal progenitors as they initiate neuronal differentiation, and may function in regulating cell cycle exit downstream of proneural bHLH factors during retinal development.
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