Bitgood M J, Shen L, McMahon A P
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Curr Biol. 1996 Mar 1;6(3):298-304. doi: 10.1016/s0960-9822(02)00480-3.
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.
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.
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.
在哺乳动物中，睾丸发育始于胚胎期，由支持细胞前体中性别决定基因Sry的表达所引发。随后，支持细胞被认为在雄性特异性细胞相互作用中发挥核心作用，包括精子发生过程中的那些相互作用。然而，这些相互作用的分子本质却知之甚少。沙漠刺猬因子（Dhh）编码一种在睾丸而非卵巢中表达的信号分子，因此可能在精子发生的调控中发挥作用。
Dhh的表达在Sry激活后不久就在支持细胞前体中开始，并在睾丸中持续到成年期。Dhh基因敲除纯合子雌性小鼠没有明显的表型，而雄性小鼠虽然存活但不育，原因是完全没有成熟精子。对不同遗传背景下发育中的睾丸进行检查表明，Dhh调节精子发生的早期和晚期阶段。Patched是刺猬信号通路的一个可能靶点，在性腺中也显示出雄性特异性转录。这种表达仅限于第二种体细胞谱系，即睾丸间质细胞。在Dhh突变体中，Patched的表达缺失。
支持细胞前体中Dhh的表达是雄性性别分化的最早迹象之一。对基因敲除突变体的分析表明，Dhh信号在哺乳动物精子发生的调控中起重要作用。Dhh突变体中Patched表达的缺失表明果蝇和小鼠之间的刺猬信号通路存在保守性，并表明睾丸间质细胞可能是Dhh信号的直接靶点。
