Turning on the male – SRY, SOX9 and sex determination in mammals

Abstract

The decision of the bi-potential gonad to develop into either a testis or ovary is determined by the presence or absence of the Sex-determining Region gene on the Y chromosome (SRY). Since its discovery, almost 13 years ago, the molecular role that SRY plays in initiating the male sexual development cascade has proven difficult to ascertain. While biochemical studies of clinical mutants and mouse genetic models have helped in our understanding of SRY function, no direct downstream targets of SRY have yet been identified. There are, however, a number of other genes of equal importance in determining sexual phenotype, expressed before and after expression of SRY. Of these, one has proven of central importance to mammals and vertebrates, SOX9. This review describes our current knowledge of SRY and SOX9 structure and function in the light of recent key developments.

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…Associations between other Y chromosome genes including SRY (Sex Determining Region) and TSPY (testis-specific protein Y-encoded) and male infertility have also been recently established. Deletion of the SRY gene occurs in 15 % of 46 XY sex reversed females [76]. Additionally, mutations in SRY gene have also been reported in 10-15 % of 46 XY males with gonadal dysgenesis [77].…”

Novel DMRT1 3'UTR+11insT mutation associated to XY partial gonadal dysgenesis

“…The Y-chromosome-located SRY gene encodes a small testis-specific protein containing a DNA-binding motif known as the HMG (high mobility group) box. However, mutations in SRY are not frequent especially in cases of 46,XY partial gonadal dysgenesis (6,7).…”

NHERF2/SIP-1 Interacts with Mouse SRY via a Different Mechanism than Human SRY

“…In mammals, testicular differentiation is under the control of the Y chromosome-encoded master switch gene SRY (1)(2)(3), which instructs the supporting cell precursors to become Sertoli cells rather than granulosa cells (4). The differentiation of Sertoli cells is thought to then drive the differentiation of the remaining cell lineages down the testis development pathway giving rise to an embryonic testis able to produce anti-Mullerian hormone and male steroid hormones (5).…”

“…The SRY gene is the founding member of the SOX gene family, all of which encode a 79-amino acid DNA binding domain called the HMG 4 domain. The HMG domain shares homology with the high mobility group proteins, which include the T cell-specific transcription factor (6).…”