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SRY (sex determining region Y)-box 1 (Gene SOX1) Homo sapiensSRY (sex determining region Y)-box 1 (Sox1), Sox2 and Sox3 are members of subgroup B1 of the Sox gene family of transcription factors, Kiefer JC (2007). The Sox family members are HMG-box containing transcription factors related to mammalian testis determining factor, SRY. Subgroups B1 and B2 (Sox14, Sox21) are involved in activation and repression of neurogenesis, respectively. Group B Sox genes have overlapping expression domains in tissues such as the optic tectum, spinal cord, inner ear, alimentary tract and branchial arches. The SOX1 (map locus 13q34) gene product, Sox-1 protein, is a 387 AA (38.9 kDa) high mobility group (HMG box) domain containing transcription factor. HMG box domains preferentially bind to and distort DNA without sequence specificity. Sox1 contains poly-Gly and poly-Ala segments. The human Sox1 gene was mapped and cloned by Malas S, et al. (1997). Sox1 is recognized as an early marker for neuroectoderm phenotype. Primitive neuroepithelia represents the earliest neural cells that possess the potential to differentiate to regionally specific neural progenitors. Sox1 is one of the earliest transcription factors expressed in ectoderm cells committed to a neural fate. The first Sox1 transcripts are detected in the neural fold ectoderm at the headfold stage, Wood HB and Episkopou V. (1999). Its appearance coincides with onset of induction of neural ectoderm where it defines dividing neural precursors of the embryonic CNS, Pevny LH et al. (1998). Sox1 is a marker for neuroectodermal cells that are differentiated past the point where they can be directed by retinoic acid (RA) and sonic hedgehog (Shh) into spinal motorneurons, Li XJ et al. (2005) Sox1 along with FGFR4 are considered to be putative neural stem cell markers. Sox1 expression is restricted within the CNS where it along with Delta, Serrate and Pax genes is believed to play a role in defining developmental fate of cells along the dorsoventral axis, Rex M, et al. (1997). Sox1 expression in animal cap explants is induced by BMP signaling. Vascular endothelial growth factor (VEGF), a potent mitogen for vascular endothelial cells, may also support neuroectodermal differentiation marked by Sox1 and Nestin expression during germ layer formation in embryoid bodies, Kim BK, et al. (2006). Sox1, -2 and - 3 maintain precursor neural cells in an undifferentiated state, Bylund M, et al. (2003) whereas proneural helix-loop-helix (bHLH) proteins induce neural differentiation. The fate of the precursor neural cells depends upon the balance of these opposing forces, Bylund M et al. (2003). Overexpression of Sox1 but not Sox2 or Sox3 in cultured neural progenitor cells is sufficient to induce neuronal lineage commitment. Sox1 binds directly to the Hes1 promoter and suppresses Hes1 transcription, thus attenuating Notch signaling. Sox1 also binds to beta-catenin and suppresses beta-catenin-mediated TCF/LEF signaling, thus potentially attenuating the wnt signaling pathway. The C-terminus of Sox1 is required for both of these interactions. Sox1 also promotes exit of cells from cell cycle and up-regulates transcription of the proneural bHLH transcription factor neurogenin 1 (ngn1), Kan L, et al. (2004). Sox1 positive cells differentiate into various neuroectodermal lineages including neural, glial, Kitajima H, et al. (2005), Barraud P, et al. (2005); and lens fiber cells, Kim JI, et al. (1999) and into early mesenchymal stem cells (MSC), Takashima Y, et al. (2007). Mesenchymal stem cells (MSC) are precursors of many mesenchymal cell lineages. The earliest transient waves of mesenchymal stem cells found in the embryonic trunk are derived from Sox1+ neuroepithelium (neural crest), Takashima Y, et al. (2007). The differentiation of dopamine (DA) producing neural cells from stem cells is of great interest because of their potential use in Parkinson’s disease mediation or cure. Sox1 is an important gene in the differentiation pathway from stem cells to dopaminergic neurons. Sox1 expression supports the propagation of undifferentiated ES cells; however upon release from self-renewal by other factors it promote differentiation into neuroectoderm at the expense of mesoderm and endoderm, Zhao S, et al. (2004), Kan L, et al. (2007). The differentiation of mESC cells into telencephalic precursor cells (Bf1+) requires suppression of Wnt and Nodal signaling by Dkk1 and LeftyA respectively, Watanabe K et al. (2005). Sox1+ appearance in hESC-derived neuroepithelial cells marks a stage when differentiation induced by FGF8 plus SHH leads to dopaminergic (TH-positive) neurons (DA) that the lack midbrain marker engrailed 1 (EN1), Yan Y, et al. (2005); Sox1 may be a signal for ventral midbrain DA development. Early exposure to Shh induces the expression of ventral markers Isl1, Nkx2.2, and Nkx6.1. Sox1 is expressed at high levels in the majority of telencephalic neurons that constitute the ventral striatum (VS). Malas S, et al. (2003) reported that Sox1 is essential for ventral telencephalic development. Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability. Sigma offers antibodies, shRNAs and other products useful for the study of the SOX1 gene products.. References: Barraud P, et al. (2005) Isolation and characterization of neural precursor cells from the Sox1-GFP reporter mouse. Eur J Neurosci. 22: 1555-1569. |
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