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M. L. Vetter, W. Chen, G. Wang, C. M. Dooley; Expression of the Proneural Target Gene Sbt1 During Mouse Eye Development. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3091.
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Proneural basic helix-loop helix (bHLH) transcription factors are key regulators of retinal neurogenesis, and they function by activating the expression of target genes that execute a program of neuronal differentiation within progenitors. In a previous screen for proneural target genes in Xenopus we identified a novel gene called sbt1 (shared bHLH target 1) and then showed that it is required for retinal neurogenesis in Xenopus. To determine the role of sbt1 during mouse eye development we sought to identify a mouse orthologue of sbt1 and investigate its expression in the developing mouse eye and other regions of the nervous system.
Mouse sbt1 (msbt1) was identified as a full-length RIKEN cDNA encoding a predicted protein of 207 amino acids with significant homology to Xenopus SBT1. We performed in situ hybridization to detect msbt1 expression from e10.5 to P0 and in the adult brain. For analysis of retinal expression in situ hybridization was performed on whole mount embryos, dissected eyes or isolated neural retina tissue, then the tissue was embedded and cryosectioned. For analysis of adult brain, in situ hybridization was performed on sections. To determine whether msbt1 function is conserved we injected Xenopus embryos with msbt1 RNA together with RNA for GFP into one blastomere at the 16-32 cell stage and assessed effects on retinal cell fates at stage 41.
Msbt1 is conserved across vertebrate species and encodes a protein that is most closely related to Xenopus SBT1 but shows no homology to any previously described protein. Msbt1 initiates expression in the dorsal central retina at approximately e12.5, in a pattern that follows Math5. By e16.5 sbt1 is expressed in a subset of progenitors, but also within the retinal ganglion cell (RGC) layer. At P0, expression in the RGC layer is robust, with weaker expression in progenitors of the neuroblastic layer. This expression differs from Xenopus, where sbt1 is transiently expressed in late progenitors or early differentiating cells but not in postmitotic retinal cells. Msbt1 was also expressed in the developing spinal cord and brain, with prominent expression in the adult neocortex. Overexpression of mouse sbt1 promoted an increase in the differentiation of early-born retinal neurons, similar to Xenopus sbt1, suggesting that its function as a regulator of neurogenesis is conserved.
Sbt1 is expressed in retinal progenitors as they initiate neuronal differentiation, but is also expressed in postmitotic retinal neurons, suggesting multiple roles for this novel protein during mouse retinal development.
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