Mechanism of sex differentiation in gonad and brain

性腺和大脑的性别分化机制

• 批准号: 11307001
• 负责人: MOROHASHI Ken-ichirou
• 金额: $ 26.18万
• 依托单位: Okazaki National Research Institutes
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11307001/
• 关键词: sex differentiation; Ad4BP; SF-1; gonad; transcription factors; XLAG; β-catenin; シグナル

Sexes are determined by composition of sex chromosomes, which is occurred at fertilization. Thereafter, sexually indifferent gonads differentiate into testis or ovary according to the sex chromosomes. Sex hormones synthesized and secreted from the gonads are known to play pivotal roles for sex differentiation of whole body. Thus, when considering sex differentiation of all animal species, it is well accepted that the key step for sex differentiation is the gonad sex determination. Thus, we have studied the molecular mechanism underlying the gonad differentiation by focussing on molecules interacting with Ad4BP/SF-l which is essential for gonad differentiation. Through yeast two hybrid screening, a number of molecules have been isolated, some of which encode transcription factors and other of which encode factors implicated in signal transduction through cell growth factors. One of the transcription factors has a paired homeo domain, and the functional significance was clearly revealed by investigating the gene disrupted mouse and by finding a human disease(XLAG) caused by the gene mutation. As a molcule for signal transduction, p-catenin was isolated. Functional analysis indicated that P-catenin activated Ad4BP/SF-l mediated transcription through a direct interaction. These findings help us to understand the molecular mechanisms underlying gonad sexdifferentiation

性别是由受精时发生的性染色体的组成决定的。此后，性冷漠的性腺根据性染色体分化为睾丸或卵巢。众所周知，性腺合成和分泌的性激素对于全身的性别分化起着关键作用。因此，在考虑所有动物物种的性别分化时，人们普遍认为性别分化的关键步骤是性腺性别决定。因此，我们通过关注与性腺分化所必需的Ad4BP/SF-1相互作用的分子来研究性腺分化的分子机制。通过酵母二杂交筛选，分离出许多分子，其中一些编码转录因子，另一些编码与细胞生长因子的信号转导有关的因子。其中一个转录因子具有配对的同源结构域，通过研究基因破坏的小鼠并发现由该基因突变引起的人类疾病（XLAG），清楚地揭示了其功能意义。作为信号转导的分子，p-连环蛋白被分离出来。功能分析表明P-连环蛋白通过直接相互作用激活Ad4BP/SF-1介导的转录。这些发现有助于我们了解性腺性别分化的分子机制

项目成果

Rina Kimura, et al.: "Identification of Novel First Exons in Ad4BP/SF-1 (NR5A1) Gene, and Their Tissue-and Soecies-Specific Usage"Biochem. Biophys. Res. Commun.. 278. 63-71 (2000)

Rina Kimura 等人：“Ad4BP/SF-1 (NR5A1) 基因中新的第一个外显子的鉴定及其组织和社会特异性用途”Biochem。

Shimono A et al: "N-myc-dependen repression of ndr1 a gene identified by direct subtraction of. 1whole mouse embryo cDNAs between wild type and N-myc mutant."Mech Dev.. 83(1-2). 39-52 (1999)

Shimono A 等人：“ndr1 基因的 N-myc 依赖性抑制，通过直接减去野生型和 N-myc 突变体之间的整个小鼠胚胎 cDNA 来鉴定。”Mech Dev.. 83(1-2)。

Akihiko Shimono, et al: "Isolation of novel cDNAs by subtractions between the anterior mesendoderm of single mouse gastrula stage embryos"Developmental Biology. 209. 369-380 (1999)

Akihiko Shimono 等人：“通过在单个小鼠原肠胚阶段胚胎的前中内胚层之间进行扣除来分离新的 cDNA”发育生物学。

Ken Kawabe, et al.: "Dax-1 as One of the Target Genes of Ad4BP/SF-1"Mol. Endocrinol.. 13. 1267-1284 (1999)

Ken Kawabe 等人：“Dax-1 作为 Ad4BP/SF-1 的靶基因之一”Mol。

Hirotaka Shibata, et al.: ""Expression profiles of COUP-TF, DAX-1 and SF-1 in the human adrenal gland and adrenocortical tumors : Possible implications in steroidoqenesis"Mol. Genet. Metab.. 74. 206-216 (2001)

Hirotaka Shibata 等人：“人肾上腺和肾上腺皮质肿瘤中 COUP-TF、DAX-1 和 SF-1 的表达谱：类固醇生成的可能影响”Mol. Genet. Metab.. 74. 206-216（