Sertoli cell signaling by Desert hedgehog regulates the male germline
Sertoli cell signaling by Desert hedgehog regulates the male germline
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DOI：
10.1016/s0960-9822(02)00480-3
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发表时间：
1996-03-01
期刊：
影响因子：
9.2
通讯作者：
McMahon, AP
中科院分区：
文献类型：
--
作者：
Bitgood, MJ;Shen, LY;McMahon, AP
背景：在哺乳动物中，睾丸的发育是在胚胎中开始的，是对支持细胞前体中性别决定基因Sry的表达的反应。随后，支持细胞被认为在男性特异性细胞相互作用中起核心作用，包括在精子发生过程中发生的相互作用。然而，人们对这些相互作用的分子性质知之甚少。沙漠刺猬（Dhh）编码一种在睾丸中表达的信号分子，而不是在卵巢中表达，因此可能在精子发生的调节中发挥作用。结果：在Sry激活后不久，Dhh在支持细胞前体中开始表达，并在睾丸中持续到成年。纯合Dhh-null突变的雌性小鼠没有明显的表型，而雄性小鼠由于完全没有成熟精子，可以存活但不能生育。补丁，一个可能的目标刺猬信号，也显示雄性特异性转录在性腺。这种表达仅限于第二种体细胞谱系，即间质细胞。结论：Dhh在pre-Sertoli细胞中的表达是男性性别分化的最早标志之一。对一个零突变体的分析表明，Dhh信号在哺乳动物精子发生的调控中起着重要作用。Dhh突变体中补丁表达的缺失提示了果蝇和小鼠之间Hedgehog信号通路的保守性，并提示间质细胞可能是Dhh信号通路的直接靶点。
Background: In mammals, testis development is initiated in the embryo in response to the expression of the sex determining gene, Sry, in Sertoli cell precursors. Subsequently, Sertoli cells are thought to play a central role in male-specific cell interactions, including those that occur during spermatogenesis. However, the molecular nature of these interactions is poorly understood. Desert hedgehog (Dhh) encodes a signaling molecule expressed in the testis, but not the ovary, and may therefore play a role in the regulation of spermatogenesis.Results: Dhh expression is initiated in Sertoli cell precursors shortly after the activation of Sry and persists in the testis into the adult, Female mice homozygous for a Dhh-null mutation show no obvious phenotype, whereas males are viable but infertile, owing to a complete absence of mature sperm, Examination of the developing testis in different genetic backgrounds suggests that Dhh regulates both early and late stages of spermatogenesis. Patched, a likely target of Hedgehog signaling, also displays male-specific transcription in the gonad. This expression is restricted to a second somatic lineage, the Leydig cells. The expression of Patched is lost in Dhh mutants,Conclusions: Dhh expression in pre-Sertoli cells is one of the earliest indications of male sexual differentiation. Analysis of a null mutant demonstrates that Dhh signaling plays an essential role in the regulation of mammalian spermatogenesis. Loss of Patched expression in Dhh mutants suggests a conservation in the Hedgehog signaling pathway between flies and mice, and indicates that Leydig cells may be the direct target of Dhh signaling.