Sex determination and the Y chromosome

Although SRY was first identified 10 years ago, we still know remarkably li ttle about its mode of action or downstream target genes. Recently, potenti al protein partners have been identified and there has been considerable ac tivity to understand the roles of WT1, SF-1, DAX-1 and SOX9 in gonadogenesi s. The emerging picture is one of complex interactions, involving both posi tive and negative regulatory signals that, depending on the cellular and pr omoter context, drive the expression of male-specific genes. Despite recent advances, however, we are still unable to explain the genetic cause of mos t cases of 46,XY gonadal dysgenesis or even a single case of Y-chromosome-n egative 46,XX maleness. (C) 2000 Wiley-Liss, Inc.