The LIM homeobox gene Lhx9 is essential for mouse gonad formation
The LIM homeobox gene Lhx9 is essential for mouse gonad formation
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DOI：
10.1038/35002622
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发表时间：
2000-02-24
期刊：
影响因子：
64.8
通讯作者：
Westphal, H
中科院分区：
文献类型：
--
作者：
Birk, OS;Casiano, DE;Westphal, H
在哺乳动物的胚胎发育过程中，卵巢和睾丸是由作为中性性腺的泌尿生殖嵴的体细胞发育而来的，其中含有迁移到那里的原始生殖细胞。在性腺性别决定后，睾丸产生睾酮和抗苗勒管激素，它们介导雄性性分化，而雌性发育途径在它们缺失的情况下增强（1-3）。在这里，我们表明，转录的LIM同源框基因Lhx 9存在于小鼠胚胎第9.5天的泌尿生殖嵴，后来他们定位到间质区的形态分化发生。在缺乏Lhx 9功能的小鼠中，生殖细胞正常迁移，但生殖嵴的体细胞无法增殖，并且无法形成离散的性腺。在没有睾酮和抗苗勒管激素的情况下，遗传上雄性小鼠在表型上是雌性的。类固醇生成因子1（Sf 1），性腺发育所必需的核受体2，在Lhx 9缺陷的生殖嵴中的表达降低到最低水平，表明Lhx 9可能位于Sf 1的上游，在发育级联中。与缺乏其他介导性腺发生早期阶段的基因的小鼠不同（4-6），Lhx 9突变体不表现出额外的主要发育缺陷。因此，LHX 9突变可能是人类某些形式的孤立性腺发育不全的基础。
During mammalian embryonic development, the ovaries and testes develop from somatic cells of the urogenital ridges as indifferent gonads, harbouring primordial germ cells that have migrated there. After sex determination of the gonads, the testes produce testosterone and anti-Mullerian hormone which mediate male sexual differentiation, and the female developmental pathway ensues in their absence(1-3). Here we show that transcripts of the LIM homeobox gene Lhx9 are present in urogenital ridges of mice at embryonic day 9.5; later they localize to the interstitial region as morphological differentiation occurs. In mice lacking Lhx9 function, germ cells migrate normally, but somatic cells of the genital ridge fail to proliferate and a discrete gonad fails to form. In the absence of testosterone and anti-Mullerian hormone, genetically male mice are phenotypically female. The expression of steroidogenic factor 1 (Sf1), a nuclear receptor essential for gonadogenesis2, is reduced to minimal levels in the Lhx9-deficient genital ridge, indicating that Lhx9 may lie upstream of Sf1 in a developmental cascade. Unlike mice lacking other genes that mediate early stages of gonadogenesis(4-6), Lhx9 mutants do not exhibit additional major developmental defects. Thus, LHX9 mutations may underlie certain forms of isolated gonadal agenesis in humans.