Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during mouse gonadal development and is a potent activator of the Müllerian inhibiting substance promoter.
Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during mouse gonadal development and is a potent activator of the Müllerian inhibiting substance promoter.
复制标题
DOI：
--
复制
发表时间：
1998-07
期刊：
影响因子：
4.6
通讯作者：
Robert S Viger;C. Mertineit;J. Trasler;M. Nemer
中科院分区：
文献类型：
--
作者：
Robert S Viger;C. Mertineit;J. Trasler;M. Nemer
哺乳动物性腺发育和性别分化是一个复杂的过程，需要一组特定的基因在严格的时空方式协调表达。虽然这些基因中的一些已被确定，分子途径，包括转录因子，是至关重要的谱系承诺和性二型性的早期事件，仍然知之甚少。加塔-4是加塔转录因子家族的成员，存在于性腺中，并且可能是性腺基因表达的调节因子。我们通过免疫组织化学分析了性腺加塔-4表达的个体发生。加塔-4蛋白在XX和XY小鼠胚胎的原始性腺中早在胚胎第11.5天就被检测到。在两种性别中，加塔-4特异性标记发育中的体细胞谱系（睾丸中的Sertoli和卵巢中的颗粒细胞），但不标记原始生殖细胞。有趣的是，丰富的加塔-4的表达保持在整个胚胎发育的支持细胞，但显着下调后不久，胚胎第13.5天的卵巢组织分化。这种表达模式表明，加塔-4可能参与早期性腺发育和可能的性二型性。与此假设一致，我们发现含有保守加塔元件的苗勒管抑制物质启动子是加塔-4的下游靶标。因此，转录因子加塔-4可能是控制哺乳动物性腺发育和性别分化的调节子级联反应中的一个新因子。
Mammalian gonadal development and sexual differentiation are complex processes that require the coordinated expression of a specific set of genes in a strict spatiotemporal manner. Although some of these genes have been identified, the molecular pathways, including transcription factors, that are critical for the early events of lineage commitment and sexual dimorphism, remain poorly understood. GATA-4, a member of the GATA family of transcription factors, is present in the gonads and may be a regulator of gonadal gene expression. We have analyzed the ontogeny of gonadal GATA-4 expression by immunohistochemistry. GATA-4 protein was detected as early as embryonic day 11.5 in the primitive gonads of both XX and XY mouse embryos. In both sexes, GATA-4 specifically marked the developing somatic cell lineages (Sertoli in testis and granulosa in ovary) but not primordial germ cells. Interestingly, abundant GATA-4 expression was maintained in Sertoli cells throughout embryonic development but was markedly down-regulated shortly after the histological differentiation of the ovary on embryonic day 13.5. This pattern of expression suggested that GATA-4 might be involved in early gonadal development and possibly sexual dimorphism. Consistent with this hypothesis, we found that the Müllerian inhibiting substance promoter which harbors a conserved GATA element is a downstream target for GATA-4. Thus, transcription factor GATA-4 may be a new factor in the cascade of regulators that control gonadal development and sex differentiation in mammals.