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

Mammalian sex-determination and differentiation are controlled by several g enes, such as Sry, Sox-9, Dax-1 and Mullarian inhibiting substance (MIS), b ut their upstream and downstream genes are largely unknown. Ad4BP/SF-1, enc oding a zinc finger transcription factor, plays important roles in gonadoge nesis. Disruption of this gene caused disappearance of the urogenital syste m including the gonad. Ad4BP/ SF-1, however, is also involved in the sex di fferentiation of the gonad at later stages, such as the regulation of stero id hormones and MIS. Pod-1/Capsulin, a member of basic helix-loop-helix tra nscription factors, is expressed in a pattern closely related but mostly co mplimentary to that of the Ad4BP/SF-1 expression in the developing gonad. I n the co-transfection experiment using cultured cells, overexpression of Po d-1/Capsulin repressed expression of a reporter gene that carried the upstr eam regulatory region of the Ar4BP/SF-1 gene. Furthermore, forced expressio n of Pod-1/Capsulin repressed expression of Ad4BP/SF-1 in the Leydig cell d erived I-10 cells. These results suggest that Pod-1/Capsulin may play impor tant roles in the development and sex differentiation of the mammalian gona d via transcriptional regulation of Ad4BP/SF-1. (C) 2001 Elsevier Science I reland Ltd. All rights reserved.