US EPA

1341233 

Journal Article 

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

Bielinska, M; Seehra, A; Toppari, J; Heikinheimo, M; Wilson, DB 

2007 

Yes 

Developmental Dynamics
ISSN: 1058-8388
EISSN: 1097-0177 

236 

1 

203-213 

17096405 

10.1002/dvdy.21004 

WOS:000243466400018 

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 Rosa26 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(-/-) 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. 

gonads; steroidogenesis; teratoma; testis; transcription factor