Disrupted gonadogenesis and male-to-female sex reversal in Pod1 knockout mice
Disrupted gonadogenesis and male-to-female sex reversal in Pod1 knockout mice
复制标题
DOI：
10.1242/dev.01266
复制
发表时间：
2004-08-01
期刊：
影响因子：
4.6
通讯作者：
Quaggin, SE
中科院分区：
文献类型：
--
作者：
Cui, SY;Ross, A;Quaggin, SE
生殖器和/或性腺发育的先天性缺陷发生在1000人中的I1，但在大多数情况下，这些缺陷的分子基础仍然不确定。我们发现，基本的螺旋-环-螺旋转录因子Pod 1（capsulin/epicardin/Tcf 21）是必不可少的睾丸和卵巢的正常发育，因此性别分化。Pod 1基因敲除（KO）小鼠的性腺明显发育不良，XX和XY小鼠的泌尿生殖道在整个胚胎发生过程中仍然无法区分。在Pod 1 KO性腺内，表达胆固醇侧链裂解酶（Scc）的细胞数量显著增加。生物化学和遗传学方法表明，Pod 1转录抑制类固醇生成因子1（Sf 1/Nr 5a 1/Ad 4 BP），孤儿核受体，调节多个基因（包括Scc）的表达，介导性分化。我们的研究结果表明，Pod 1是性腺发育所必需的，并将其置于一个转录网络中，该网络协调性腺祖细胞的细胞命运决定。
Congenital defects in genital and/or gonadal development occur in I1 in 1000 humans, but the molecular basis for these defects in most cases remains undefined. We show that the basic helix-loop-helix transcription factor Pod1 (capsulin/epicardin/Tcf21) is essential for normal development of the testes and ovaries, and hence for sexual differentiation. The gonads of Pod1 knockout (KO) mice were markedly hypoplastic, and the urogenital tracts of both XX and XY mice remained indistinguishable throughout embryogenesis. Within Pod1 KO gonads, the number of cells expressing the cholesterol side-chain cleavage enzyme (Scc) was increased markedly. Biochemical and genetic approaches demonstrated that Pod1 transcriptionally represses steroidogenic factor 1 (Sf1/Nr5a1/Ad4BP), an orphan nuclear receptor that regulates the expression of multiple genes (including Scc) that mediate sexual differentiation. Our results establish that Pod1 is essential for gonadal development, and place it in a transcriptional network that orchestrates cell fate decisions in gonadal progenitors.