Pod-1/Capsulin shows a sex- and stage-dependent expression pattern in the mouse gonad development and represses expression of Ad4BP/SF-1.

Abstract Mammalian sex-determination and differentiation are controlled by several genes, such as Sry , Sox-9 , Dax-1 and Mullerian inhibiting substance ( MIS ), but their upstream and downstream genes are largely unknown. Ad4BP/SF-1 , encoding a zinc finger transcription factor, plays important roles in gonadogenesis. Disruption of this gene caused disappearance of the urogenital system including the gonad. Ad4BP/SF-1 , however, is also involved in the sex differentiation of the gonad at later stages, such as the regulation of steroid hormones and MIS . Pod-1/Capsulin , a member of basic helix–loop–helix transcription factors, is expressed in a pattern closely related but mostly complimentary to that of the Ad4BP/SF-1 expression in the developing gonad. In the co-transfection experiment using cultured cells, overexpression of Pod-1/Capsulin repressed expression of a reporter gene that carried the upstream regulatory region of the Ad4BP/SF-1 gene. Furthermore, forced expression of Pod-1/Capsulin repressed expression of Ad4BP/SF-1 in the Leydig cell-derived I-10 cells. These results suggest that Pod-1/Capsulin may play important roles in the development and sex differentiation of the mammalian gonad via transcriptional regulation of Ad4BP/SF-1 .