GATA-4 is required for sex steroidogenic cell development in the fetal mouse

Malgorzata Bielinska, Amrita Seehra, Jorma Toppari, Markku Heikinheimo, David B. Wilson

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

The transcription factor GATA-4 is expressed in Sertoli cells, steroidogenic Leydig cells, and other testicular somatic cells. Previous studies have established that interaction between GATA-4 and its cofactor FOG-2 is necessary for proper Sry expression and all subsequent steps in testicular organogenesis, including testis cord formation and differentiation of both Sertoli and fetal Leydig cells. Since fetal Leydig cell differentiation depends on Sertoli cell-derived factors, it has remained unclear whether GATA-4 has a cell autonomous role in Leydig cell development. We used two experimental systems to explore the role of GATA-4 in the ontogeny of testicular steroidogenic cells. First, chimeric mice were generated by injection of Gata4-/- ES cells into Rosa28 blastocysts. Analysis of the resultant chimeras showed that in developing testis Gata4-/- cells can contribute to fetal germ cells and interstitial fibroblasts but not fetal Leydig cells. Second, wild-type or Gata4-/- ES cells were injected into the flanks of intact or gonadectomized nude mice and the resultant teratomas examined for expression of steroidogenic markers. Wild-type but not Gata4-/-ES cells were capable of differentiating into gonadal-type steroidogenic lineages in teratomas grown in gonadectomized mice. In chimeric teratomas derived from mixtures of GFP-tagged Gata4+/+ ES cells and unlabeled Gata4-1- ES cells, sex steroidogenic cell differentiation was restricted to GFP-expressing cells. Collectively these data suggest that GATA-4 plays an integral role in the development of testicular steroidogenic cells.

Original languageEnglish
Pages (from-to)203-213
Number of pages11
JournalDevelopmental Dynamics
Volume236
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Gonads
  • Steroidogenesis
  • Teratoma
  • Testis
  • Transcription factor

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