Steroidogenic factor 1 and Dax-1 colocalize in multiple cell lineages: potential links in endocrine development.
Mutations of the orphan nuclear receptors, steroidogenic factor 1 (SF-1) and DAX-1, cause complex endocrine phenotypes that include impaired adrenal development and hypogonadotrophic hypogonadism. These similar phenotypes suggest that SF-1 and DAX-1 act in the same pathway(s) of endocrine development. To explore this model, we now compare directly their sites of expression. In mouse embryos, SF-1 expression in the urogenital ridge and brain either preceded or coincided with Dax-1 expression, with coordinate expression thereafter in the adrenal cortex, testis, ovary, hypothalamus, and anterior pituitary. The striking colocalization of SF-1 and Dax-1 supports the model that they are intimately linked in a common pathway of endocrine development. The slightly earlier onset of SF-1 expression and its ability to bind specifically to a conserved sequence in the Dax-1 5'-flanking region suggested that SF-1 may activate Dax-1 expression. However, promoter activity of Dax-1 5'-flanking sequences did not require this potential SF-1-responsive element, and Dax-1 expression was unimpaired in knockout mice lacking SF-1, establishing that SF-1 is not required for Dax-1 gene expression in these settings. Although the precise mechanisms remain to be established and may be multifactorial, our results strongly suggest that these two orphan nuclear receptors interact in a common pathway of endocrine development.
Ikeda
Y
Y
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Swain
A
A
Weber
T J
TJ
Hentges
K E
KE
Zanaria
E
E
Lalli
E
E
Tamai
K T
KT
Sassone-Corsi
P
P
Lovell-Badge
R
R
Camerino
G
G
Parker
K L
KL
D000818:Animals; D019070:Cell Lineage; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D004702:Endocrine Glands / Q000196:embryology*; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins; D017403:In Situ Hybridization; D051379:Mice; D009154:Mutation; D009928:Organ Specificity; D011247:Pregnancy; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid / Q000032:analysis* / Q000235:genetics; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C539966:Nr0b1 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse