Vincent R Harley

..Many genes, however, remain unidentified, because in the majority of cases of XY females and in all cases of XX males lacking SRY, the mutated gene is unknown...

..This study documents cases of human disease being explained, at a molecular level, by the impaired ability of a protein to accumulate in the nucleus...

..CaM recognition could underlie XY sex reversal. Given that the CaM-binding region of SRY is well-conserved among high mobility group box proteins, CaM-dependent nuclear import may underlie additional disease states...

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..These results indicate the importance of CaM for SRY nuclear import, transcriptional activity, testis differentiation, and sex determination...

..In cultured cells, increasing levels of DAX1 antagonized SF1-, SF1/SRY-, and SF1/SOX9-mediated activation of TES, due to reduced binding of SF1 to TES, providing a likely mechanism for DSS...

..E. lutescens/E. tancrei and E. fuscocapillus could have independently stabilized their sex determination mechanisms by Sry-independent and Sry-dependent approaches, respectively...

..Our data support a model in ovary development whereby activation of β-catenin prevents Sf1 binding to the Sox9 enhancer, thereby inhibiting Sox9 expression and Sertoli cell differentiation...

..In summary, we provide evidence that FGFR2 is important for male sex determination in mice, thereby rendering human FGFR2 a candidate gene for unsolved DSD cases such as 10q26 deletions...

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..In mice, Sox9 regulation is under the transcriptional control of SRY, SF1 and SOX9 via a conserved testis-specific enhancer of Sox9 (TES). Regulation of SOX9 in human sex determination is however poorly understood...

..SOX13 is also detected in the developing kidney, pancreas, and liver as well as in the visceral mesoderm of the extra-embryonic yolk sac and spongiotrophoblast layer of the placenta...

..The findings suggest that ATRX in humans may play a role in adult spermatogenesis as well as in testicular development...

..A campomelic dysplasia patient with SOX9 mutation outside the NLS regions also showed defective SOX9 nuclear import implying that nuclear import defects could be a common explanation for SRY and SOX9 HMG domain mutations...

..SRY and SOX9 proteins have been characterized extensively and aspects of their function and regulation are now known...

..Our results indicate that the regulation of Rhox gene expression and its potential function during embryogenesis are quite distinct from those previously reported for Rhox gene regulation in postnatal gonads...

..We propose that there is a threshold level of SRY activity or expression required for testis determination, as we observe that familial mutations have the least effect on SRY activity...

..Further identification of critical downstream effectors of the Wnt4 signaling pathway in mouse models and in patients with sex-reversal conditions could help in understanding sex-reversal pathologies in humans...

..Here we review extensively the SOX protein interactions with partner co-factors, the ability of SOX proteins to modulate Wnt signalling and the effect of post-translational modification of SOX proteins on their function...

..Our data suggest a role for SOX13 in the specification and/or differentiation of a specific subset of neurons in the developing central nervous system...

..SRY and SOX9 mutations in DSD have uncovered regulatory sites for sumoylation, ubiquitination, acetylation and phosphorylation, many of which are essential for their transport and sex determining functions...

..Specifically, we assessed the role of disease-associated repeat length polymorphisms in the androgen receptor (AR), estrogen receptor beta (ERbeta), and aromatase (CYP19) genes...

..Less well understood are mechanisms of Wnt signalling that do not involve beta-catenin stabilization and result in inhibition of beta-catenin-mediated transcription...

..The SRY gene, which is located on the Y chromosome and directs male development, may promote aggression and other traditionally male behavioural traits, resulting in the fight-or-flight reaction to stress...

..These data suggest that p54nrb plays an important role in the regulation of Sox9 function and the formation of paraspeckle bodies during chondrogenesis...

..These results establish that SOX9 cooperative dimerization is required for chondrogenesis but not for sex determination and may explain why campomelic dysplasia need not be associated with XY sex reversal...

..Alignment of vertebrate ATRX sequences highlights other conserved elements, including a negatively charged mammalian sequence which we propose to be involved in binding of positively charged histone tails...

..The conservation and loss of particular motifs identify those required for testicular function (ATRY) and function in other tissues (ATRX)...

..In vitro assays demonstrate that the C200W mutant retains the ability to functionally interact with SF1, which suggests that SF1-independent interactions of DAX1 could be responsible for the import defect...

..These results demonstrate a direct male-specific effect on the brain by a gene encoded only in the male genome, without any mediation by gonadal hormones...

..We review what is known about ATRX as a chromatin remodeling protein, and its role in mammalian sex differentiation...

..Therefore, perhaps DAX1/Dax1 acts within a 'window' of activity, outside of which testis formation does not occur. Here, we discuss the function and possible mechanisms of DAX1 action in male gonadogenesis...

..Tmem184a expression is further shown to be expressed exclusively within the Sertoli cells of the developing testis cords, suggesting that it may mediate sex-specific signaling events during Sertoli cell differentiation...