Developm(A) ESox Amh Promoter (B) Amh Promoter Transcription upregulated (C) Amh Promoter Transcription 和对基因表达的 further upregulated Fiqure 17.8 Synergism of Sox and Sfl to activate the expression of the amh gene. (A)The binding of Sox9 to the Amh promoter initiates tran- scription of the Amh gene in the Sertoli cells. B)After Sox9 binds, the expression of AMH is upregulated by the binding of SFI and Wt-1. AMH is believed to position SFI on its DNA-binding site and Wt-1 is joined to the Sfl protein. (C)Gata(a transcription fac tor common to many cell types) upregulates Amh expression fur- ther. Neither Sfl nor Gata can function if Sox is absent. (After Arango et al. 1999
Developmental Biology Sox 和SF 对Amh 基因表达的作用
Developmental Biology 与卵巢命运决定有关的X染色体基因 Genoty X X Inactive SRY DAXI SRY DAX1:它编码细胞核激 DAXE 素受体,是X染色体上的潜在的 DAXI A 卵巢决定基因。1980年首次发现 2 copi Ies 于XY姊妹中,1994年克隆出基 DAXT 因,其性别逆转是由于2个拷贝 的DAX1可以抑制SRY的作用。 小鼠Dax1在生殖嵴细胞中表 达,它可能是拮抗Sry的活性而 下调s1的表达。 Gonads Testis Ovary Gonadal ysg Phenotype Male Female Female Figure 20.8 Phenotypic sex reversal in humans having two copies of the DAXI locus DAXI (on the X chromosome) plus SRY(on the Y) produces testes. DAXI without the SRY (since the other DAXI locus is on the inactive X chromosome) produces ovaries Two active copies of DAXI (on the active X chromosome) plus an SRY(from the Y chromosome) lead to a poorly formed gonad. Since the gonad makes neither AMH nor testosterone, the phenotype is female. (After Genetics Review Group, 1995.)
Developmental Biology DAX1：它编码细胞核激 素受体，是X染色体上的潜在的 卵巢决定基因。1980年首次发现 于XY姊妹中，1994年克隆出基 因，其性别逆转是由于2个拷贝 的DAX1可以抑制SRY的作用。 小鼠Dax1在生殖嵴细胞中表 达，它可能是拮抗Sry的活性而 下调sf1的表达。 与卵巢命运决定有关的X染色体基因
WNT4:是常染色体上的潜在的卵巢决定基因。小鼠wn4在分化前 的XX和XY生殖嵴中都表达,其后只在XX生殖腺中表达。 在Wnt4XX小鼠上,卵巢形成异常,其细胞表达Amh和睾丸酮等睾丸 特异性标记。 Sry的作用可能是抑制生殖嵴中wnt4的表达和促进S的表达。 X chromosome DAXI Y chromosome SRY Testes WNT4 Figure 17.10 Possible mechanism for primary sex determination in mammals. While we do not know the specific interactions involved, this model attempts to organize the data into a coher ent sequence. Other models are possible. In this model, SRY competes with the DAXI rotein to activate or repress the SFI gene If a single X and Y chromosome are present. the SRY will be favored, and the activation of SFI will occur. If two copies of DAX! are present on the X chromosome(or if there is no Y chromosome), the SFI gene will not be activated. The SFl protein is thought to activate the SOX9 gene, which instructs the sex cords to develop into the Sertoli cells of the testes, and may also repress WNT4 WNT4 would otherwise cause the differentiation of the gonad into an ovary. Most of the genes activated by WNT4 and soX9 have not been identified, and the mechanisms by which SRY and DAXI function are not yet known
Developmental Biology WNT4：是常染色体上的潜在的卵巢决定基因。小鼠Wnt 4在分化前 的XX和XY生殖嵴中都表达，其后只在XX生殖腺中表达。 在Wnt4-/-XX小鼠上，卵巢形成异常，其细胞表达Amh和睾丸酮等睾丸 特异性标记。 Sry的作用可能是抑制生殖嵴中Wnt4的表达和促进Sf1的表达
Developmental Biology 2. secondary sex determination 指睾丸或卵巢形成后,由它们分泌的激素来影 响性器官的发育。 在出现睾丸的胚胎中,中肾旁管( Mullerian duct)退化,而中肾管( Wolffian duct)分化为输精管、 附睾、精囊。 在出现卵巢的胚胎中,中肾管退化,中肾旁管 分化为输卵管、子宫等
Developmental Biology 2. secondary sex determination: 指睾丸或卵巢形成后，由它们分泌的激素来影 响性器官的发育。 在出现睾丸的胚胎中，中肾旁管(Mullerian duct)退化，而中肾管(Wolffian duct)分化为输精管、 附睾、精囊。 在出现卵巢的胚胎中，中肾管退化，中肾旁管 分化为输卵管、子宫等
Developmental Biology 抗中肾旁管激素(anti- Mullerian duct hormone, AMH:由睾丸支柱细胞分泌的560a糖蛋白,其作用可能是诱导 中肾旁管周围的间质细胞分泌一种促凋亡因子,使中肾旁管退化。 Mullerian duct Mullerian duct (A) Wolffian duct Wolffian duct Figure 20 duct(arrow at left)and Wolffian duct Assay for anti-Mullerian duct hormone (arrow at right) are open. B)The activity in the anterior segment of a Wolffian duct (arrow)is open, but the 14.5-day fetal rat reproductive tract after Mullerian duct has degenerated and 3 days in culture. (A) Both the Mullerian closed. Courtesy of N. Josso. cultured in the presence of fetal testis or sertoli cells
Developmental Biology 抗中肾旁管激素(anti-Mullerian duct hormone, AMH)：由睾丸支柱细胞分泌的560aa糖蛋白，其作用可能是诱导 中肾旁管周围的间质细胞分泌一种促凋亡因子，使中肾旁管退化。 cultured in the presence of fetal testis or sertoli cells. Mullerian duct Wolffian duct Mullerian duct Wolffian duct