Disease relevance of Sox3

• In humans, mutations affecting the X-linked transcription factor SOX3 are associated with hypopituitarism and mental retardation, but nothing is known of their etiology [1].

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

• Sox3 is upregulated in the posterior ectoderm during late streak and neural plate stages and is concomitantly downregulated in the chorion [8].
• During early somitogenesis, all three genes are expressed in the neuroectoderm, and Sox2 and Sox3 are also expressed in the primitive streak ectoderm, gut endoderm and prospective sensory placodes [8].
• Comparative expression of the mouse Sox1, Sox2 and Sox3 genes from pre-gastrulation to early somite stages [8].
• Sox3 expression in undifferentiated spermatogonia is required for the progression of spermatogenesis [5].
• Sox3, a member of the high mobility group (HMG) family of transcription factors, is expressed in neural progenitor cells and in the gonads [5].

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].

References