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Gene Review

Sox3  -  SRY (sex determining region Y)-box 3

Mus musculus

Synonyms: Sox-3, Transcription factor SOX-3
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Disease relevance of Sox3


High impact information on Sox3

  • Cells in the ventral diencephalon, where Sox3 is usually highly expressed, have altered properties in mutant embryos, leading to abnormal development of Rathke's pouch, which does not express the gene [1].
  • Here we report that expression of the transcription factors Sox1, Sox2 and Sox3 (Sox1-3) is a critical determinant of neurogenesis [2].
  • However, the hypoblast does induce transient expression of the early markers Sox3 and Otx2 [3].
  • This has led to the proposal that Sry evolved from Sox-3 [4].
  • Analysis of the distribution of Sox-3 RNA shows that its main site of expression is in the developing central nervous system, suggesting a role for Sox-3 in neural development [4].

Biological context of Sox3

  • In this study, we examined the expression and function of Sox3 in C57BL/6 mice to better understand its role in spermatogenesis [5].
  • Components of specific metabolic and signal transduction pathways, and several transcription factors, including Sox3, FoxM1, and PTTG1, were also enriched in neural progenitor cultures [6].
  • We also find that at least some of the regulatory sequences are able to drive expression of the transgene in the CNS Xenopus laevis embryos in a manner that reflects the endogenous Sox3 expression pattern [7].
  • To investigate the regulation of Sox3 expression we identified cis-regulatory regions in the Sox3 promoter that direct tissue-specific heterologous marker gene expression in transgenic mice [7].

Anatomical context of Sox3


Associations of Sox3 with chemical compounds

  • Different combinations of signals are responsible for different aspects of this early transient induction: FGF initiates expression of Sox3 and ERNI, retinoic acid can induce Cyp26A1 and only a combination of low levels of FGF8 together with Wnt- and BMP-antagonists can induce Otx2 [9].

Co-localisations of Sox3

  • Sox3 expression was restricted to proliferating germ cells and colocalized with neurogenin 3 (Ngn3), a helix-loop-helix transcription factor implicated in spermatogonial differentiation [5].

Other interactions of Sox3

  • Sox2 and Sox3 are expressed in the epiblast and extraembryonic ectoderm of the egg cylinder, becoming restricted to the prospective neural plate and chorion at the onset of gastrulation [8].
  • We conclude that Sox3 is expressed in A(s), A(pr) and A(al) spermatogonia and is required for spermatogenesis through a pathway that involves Ngn3 [5].
  • In animal cap assays, XmafB can induce Pax6, Xlens1 and Sox3 expression, but XL-maf fails to induce Pax6 and Xlens1 expression [10].
  • Xenopus Sox17alpha, Sox17beta, Sox3 and mouse Sox7 are reported to be negative regulators of the WNT-beta-catenin-TCF signaling pathway [11].


  1. SOX3 is required during the formation of the hypothalamo-pituitary axis. Rizzoti, K., Brunelli, S., Carmignac, D., Thomas, P.Q., Robinson, I.C., Lovell-Badge, R. Nat. Genet. (2004) [Pubmed]
  2. Vertebrate neurogenesis is counteracted by Sox1-3 activity. Bylund, M., Andersson, E., Novitch, B.G., Muhr, J. Nat. Neurosci. (2003) [Pubmed]
  3. Reconciling different models of forebrain induction and patterning: a dual role for the hypoblast. Foley, A.C., Skromne, I., Stern, C.D. Development (2000) [Pubmed]
  4. A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2. Collignon, J., Sockanathan, S., Hacker, A., Cohen-Tannoudji, M., Norris, D., Rastan, S., Stevanovic, M., Goodfellow, P.N., Lovell-Badge, R. Development (1996) [Pubmed]
  5. Sox3 expression in undifferentiated spermatogonia is required for the progression of spermatogenesis. Raverot, G., Weiss, J., Park, S.Y., Hurley, L., Jameson, J.L. Dev. Biol. (2005) [Pubmed]
  6. Global analysis of gene expression in neural progenitors reveals specific cell-cycle, signaling, and metabolic networks. Karsten, S.L., Kudo, L.C., Jackson, R., Sabatti, C., Kornblum, H.I., Geschwind, D.H. Dev. Biol. (2003) [Pubmed]
  7. Expression of Sox3 throughout the developing central nervous system is dependent on the combined action of discrete, evolutionarily conserved regulatory elements. Brunelli, S., Silva Casey, E., Bell, D., Harland, R., Lovell-Badge, R. Genesis (2003) [Pubmed]
  8. Comparative expression of the mouse Sox1, Sox2 and Sox3 genes from pre-gastrulation to early somite stages. Wood, H.B., Episkopou, V. Mech. Dev. (1999) [Pubmed]
  9. A role for the hypoblast (AVE) in the initiation of neural induction, independent of its ability to position the primitive streak. Albazerchi, A., Stern, C.D. Dev. Biol. (2007) [Pubmed]
  10. Distinct roles of maf genes during Xenopus lens development. Ishibashi, S., Yasuda, K. Mech. Dev. (2001) [Pubmed]
  11. Expression of human SOX18 in normal tissues and tumors. Saitoh, T., Katoh, M. Int. J. Mol. Med. (2002) [Pubmed]
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