Sertoli cell signaling by Desert hedgehog regulates the male germline

Curr Biol. 1996 Mar 1;6(3):298-304. doi: 10.1016/s0960-9822(02)00480-3.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Female
  • Gene Expression Regulation
  • Gene Targeting
  • Hedgehog Proteins
  • Male
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Proteins / genetics
  • Proteins / physiology*
  • Sertoli Cells / physiology*
  • Signal Transduction
  • Spermatogenesis / physiology*
  • Testis / cytology
  • Trans-Activators*


  • Hedgehog Proteins
  • Membrane Proteins
  • Proteins
  • Trans-Activators