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SRY (sex determining region Y)-box 9/Sox-9 (Gene SOX9) Homo sapiensThe SOX9 (map locus: Entrez 17q24.3-q25.1; Ensembl 17q24.3 and HGNC 17q23) gene product, SRY (sex determining region Y)-box 9/Sox-9 protein, is a 509 AA (56.1 kDa) high mobility group (HMG box) domain (105 to 173) containing transcription factor. HMG box domains preferentially bind to and distort DNA. Sox9 contains a 40 AA Gln/Pro-rich region (339 to 378) that includes a 5 AA polyproline stretch (342 to 346). TSox9, Sox8 and Sox10 comprise subgroup E of the Sox-family transcription factors. This subgroup has been linked to the specification and differentiation of a variety of epithelial tissues and its members appear as early response genes to neural crest induction. Sox-9 promotes neural-crest-like properties in neural tube progenitors rather than CNS neural differentiation and together with the other SoxE genes directs migratory crest cells away from neuronal lineages towards glial cells, precursors of astrocytes and oligodendrocyts, and melanocytes, Cheung M and Briscoe J. (2003), Hong CS, et al. (2005). Sox9 also participates in the switching from neural to glial stem cell lineages in the developing spinal cord, Stolt CC, et al. (2003) and CNS, Kordes U, et al. (2005). The role of Sox9 as a maintenance factor for progenitor lineage specific stem cell pools is starting to emerge. Sox9 is required for maintenance of the pancreatic progenitor cell pool, Seymour PA, et al. (2007), Lynn FC, et al. (2007); the retinal pool and Muller glial cells, Poche RA, et al. (2008); progenitor cells and the hair stem cell compartment, Vidal VP, et al. (2005), that participates in development of all skin epithelial lineages, Nowak JA et al. (2008) and the mesenchymal stem-cell derived osteochondroprogenitors, Zhou G, et al. (2006). Sox9 has been linked to an impressive array of differentiation and development processes. These include: chondrogenesis, Healy C, et al. (1996, 1999), Wheatley S, et al. (1996), Lefebvre V and de Crombrugghe B. (1998), Bi W, et al (1999); differentiation of Sertoli cells, Morais da Silva S, et al. (1996), Kobayashi A, et al. (2005); tooth morphogenesis (odontogenesis), Mitsiadis TA et al. (1998); invagination of the otic placode, Barrionuevo F, et al. (2008); pancreas development, Lioubinski O, et al. (2003); valvulogenesis, Akiyama H, et al. (2004), Lincoln J, et al. (2007); specification of pyloric sphincter epithelium, Moniot B, et al. (2004); tracheal cartilage ring formation, Elluru RG and Whitsett JA. (2004); development of the outer root sheath (ORS) of hair follicles and hair stem cell compartment, Vidal VP, et al. (2005); maintenance of structural integrity of the notochord (axial skeletogenesis), Barrionuevo F, et al. (2006); differentiation of intestinal Paneth cells, Mori-Akiyama Y, et al. (2007); Bastide P, et al. (2007); melanocyte differentiation and pigmentation, Cook AL, et al. (2005); Passeron T, et al. (2007); and prostate development, Thomsen MK, et al. (2008). The most exhaustively studied roles of Sox9 in development involve chondrogenesis and sex-determination. Dysregulations of Sox9 that involve loss of function mutations cause the syndrome of Campomelic Dysplasia (CD), Schafer AJ, et al. (1995); Foster JW, et al. (1996). CD is a semilethal osteochondrodysplasia characterized by skeletal malformation (bone dysmorphology) and frequently associated-autosomal male to female (46, XY females) sex-reversal, Cameron FJ, et al. (1996); conversely, overexpression of Sox9 can induce female to male (46, XX karyotype) sex-reversal, Huang B, et al. (1999). Sox9 is an important member of the mammalian sex-determination genes that includes: sex determining gene, Y (SRY), anti-Müllerian hormone (AMH), Wilms tumor gene 1 (WT1), steroidogenic factor-1 (SF1), nuclear receptor DAX-1 (DAX1) and DMRT1. Sox9 promotes development of the male phenotype. It is expressed at high levels in male but not female genital ridges and sex cords of developing testis, Kent J et al. (1996). Expression is specific to the Sertolli cell lineage, not fetal germ cells. After the coelomic epithelial cells migrate into the gonad, there is first a decision to become interstitial or supporting cells; transient expression of SRY in the supporting cells determines their fate as Sertoli cells by up-regulating Sox9, Sekido R, et al. (2004). Several researchers have reported that Sox9 expression is sufficient to induce testis formation in mammals, Vidal VP, et al. (2001); Guo JK, et al. (2002); Qin Y, et al. (2005). Sertoli cells are responsible for creating an immunoprivileged environment in the testis. Recognition of this quality has lead to an interest in using Sertoli cells in heterotopic sites to protect clinically important cells such as insulin producing pancreatic islet cells (to reverse type I diabetes) and dopaminergic (DA) neural cells (to treat Parkinson’s disease) from immune rejection. Sox9 has been proposed as a useful marker of Sertoli cells in these heterotropic transplants, Hemendinger RA, et al. (2002). Chondrogenic competence results from the cooperative function of the subgroup-E Sox genes in response to BMP signaling; subsequently, Sox9 along with Sox5 and Sox6 execute and maintain the cartilage differentiation program, a multistep process that leads to endochondral bone formation, Lefebvre V, et al. (2001), Chimal-Monroy J, et al. (2003). Sox9 becomes active in prechondrocytic mesenchymal condensations, and is maintained at high levels in differentiated chondrocytes. The regulation of Sox9 and its role in chondrogenesis is an area of intense research. Sox9 is a general marker for basal cell carcinoma (BCC) where high expression is linked to enhanced malignancy and tumor invasiveness, Vidal VP, et al. (2008); Wang, H, et al. (2008). Inappropriate ECM deposition is a hallmark of fibrosis. Since Sox9 induces the formation of extracellular matrix (ECM) components, especially collagen, a role for Sox9 in the regulation of the pathology of fibrosis has been suggested, Hanley KP, et al. (2008). Sigma offers antibodies, shRNAs and other products useful for the study of the SOX9 gene. References: Akiyama H, et al. (2004) Essential role of Sox9 in the pathway that controls formation of cardiac valves and septa. Proc Natl Acad Sci U S A. 101: 6502-6507. |
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