Genomes and Genes
Vincent R Harley
Affiliation: Monash University
- Defective importin beta recognition and nuclear import of the sex-determining factor SRY are associated with XY sex-reversing mutationsVincent R Harley
Prince Henry s Institute of Medical Research, Melbourne 3168, Victoria, Australia
Proc Natl Acad Sci U S A 100:7045-50. 2003..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...
- The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9]Vincent R Harley
Prince Henry s Institute of Medical Research, Clayton 3168, Victoria, Australia
Endocr Rev 24:466-87. 2003..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...
- Defective calmodulin-mediated nuclear transport of the sex-determining region of the Y chromosome (SRY) in XY sex reversalHelena Sim
Prince Henry s Institute of Medical Research, Level 4 Block E, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia
Mol Endocrinol 19:1884-92. 2005..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...
- Excess DAX1 leads to XY ovotesticular disorder of sex development (DSD) in mice by inhibiting steroidogenic factor-1 (SF1) activation of the testis enhancer of SRY-box-9 (Sox9)Louisa M Ludbrook
Prince Henry s Institute of Medical Research, Melbourne, Victoria 3168, Australia
Endocrinology 153:1948-58. 2012..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...
- Defective survival of proliferating Sertoli cells and androgen receptor function in a mouse model of the ATR-X syndromeStefan Bagheri-Fam
Molecular Genetics and Development Division, Prince Henry s Institute of Medical Research, Clayton, VIC 3168, Australia
Hum Mol Genet 20:2213-24. 2011....
- Inhibition of SRY-calmodulin complex formation induces ectopic expression of ovarian cell markers in developing XY gonadsHelena Sim
Molecular Genetics and Development Division, Prince Henry s Institute of Medical Research, Level 4 Block E, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne, Victoria 3168, Australia
Endocrinology 152:2883-93. 2011..These results indicate the importance of CaM for SRY nuclear import, transcriptional activity, testis differentiation, and sex determination...
- Wnt signaling in ovarian development inhibits Sf1 activation of Sox9 via the Tesco enhancerPascal Bernard
Prince Henry s Institute of Medical Research, Monash Medical Centre, P O Box 5152, Clayton, Melbourne 3168, Australia
Endocrinology 153:901-12. 2012..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...
- Sox9 gene regulation and the loss of the XY/XX sex-determining mechanism in the mole vole Ellobius lutescensStefan Bagheri-Fam
Molecular Genetics and Development Division, Prince Henry s Institute of Medical Research, Clayton, Melbourne, Victoria 3168, Australia
Chromosome Res 20:191-9. 2012..E. lutescens/E. tancrei and E. fuscocapillus could have independently stabilized their sex determination mechanisms by Sry-independent and Sry-dependent approaches, respectively...
- Loss of Fgfr2 leads to partial XY sex reversalStefan Bagheri-Fam
Human Molecular Genetics Laboratory, Prince Henry s Institute of Medical Research, Monash Medical Centre, Melbourne 3168, Australia
Dev Biol 314:71-83. 2008..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...
- A SOX9 defect of calmodulin-dependent nuclear import in campomelic dysplasia/autosomal sex reversalAnthony Argentaro
Human Molecular Genetics Laboratory, Prince Henry s Institute of Medical Research, Level 4 Block E, Monash Medical Centre, 246 Clayton Rd, Clayton, Victoria, 3168, Australia
J Biol Chem 278:33839-47. 2003....
- The human testis-determining factor SRY localizes in midbrain dopamine neurons and regulates multiple components of catecholamine synthesis and metabolismDaniel P Czech
Molecular Genetics and Development Division, Prince Henry s Institute of Medical Research, Monash Medical Centre, Melbourne, Australia
J Neurochem 122:260-71. 2012..This ancillary genetic mechanism might contribute to gender bias in fight-flight behaviours in men or their increased susceptibility to dopamine disorders, such as Parkinson's disease and schizophrenia...
- The molecular action of testis-determining factors SRY and SOX9Vincent R Harley
Prince Henry s Institute of Medical Research, Monash Medical Centre, Melbourne, Vic, Australia
Novartis Found Symp 244:57-66; discussion 66-7, 79-85, 253-7. 2002..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...
- Failure of SOX9 regulation in 46XY disorders of sex development with SRY, SOX9 and SF1 mutationsKevin C Knower
Molecular Genetics and Development, Prince Henry s Institute, Melbourne, Victoria, Australia
PLoS ONE 6:e17751. 2011..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...
- Localization of the chromatin remodelling protein, ATRX in the adult testisPaisu Tang
Prince Henry s Institute of Medical Research, Victoria 3168, Australia
J Reprod Dev 57:317-21. 2011..The findings suggest that ATRX in humans may play a role in adult spermatogenesis as well as in testicular development...
- SOX13 exhibits a distinct spatial and temporal expression pattern during chondrogenesis, neurogenesis, and limb developmentYi Wang
Human Molecular Genetics Laboratory, Prince Henry s Institute of Medical Research, 246 Clayton Rd, Victoria 3168, Australia
J Histochem Cytochem 54:1327-33. 2006..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...
- Sex with two SOX on: SRY and SOX9 in testis developmentMichael J Clarkson
Prince Henry s Institute of Medical Research, PO 5152, Clayton, Victoria 3168, Australia
Trends Endocrinol Metab 13:106-11. 2002..SRY and SOX9 proteins have been characterized extensively and aspects of their function and regulation are now known...
- The rhox homeobox gene family shows sexually dimorphic and dynamic expression during mouse embryonic gonad developmentHinda Daggag
Murdoch Children s Research Institute and Department of Pediatrics, University of Melbourne, Royal Children s Hospital, Melbourne, Victoria, Australia
Biol Reprod 79:468-74. 2008..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...
- Biochemical defects in eight SRY missense mutations causing XY gonadal dysgenesisClaire L Mitchell
Howard Florey Institute, and Department of Biochemistry, The University of Melbourne, VIC 3010, Melbourne, Australia
Mol Genet Metab 77:217-25. 2002..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...
- Transient neuroprotection by SRY upregulation in dopamine cells following injury in malesDaniel P Czech
Brain and Gender Laboratory D P C, J L, J C, H L, E K M, V R H, MIMR PHI formerly Prince Henry s Institute of Medical Research, Department of Biochemistry and Molecular Biology D P C, V R H, and Department of Anatomy and Developmental Biology J L, V R H, Monash University, Melbourne, 3168, Victoria, Australia
Endocrinology 155:2602-12. 2014..We speculate that dysregulation of SRY may contribute the susceptibility of males to PD. ..
- Wnt4 inhibits beta-catenin/TCF signalling by redirecting beta-catenin to the cell membranePascal Bernard
Human Molecular Genetics Laboratory, Prince Henry s Institute of Medical Research, Monash Medical Centre, PO Box 5152, Clayton 3168, Vic, Australia
Biol Cell 100:167-77. 2008..Less well understood are mechanisms of Wnt signalling that do not involve beta-catenin stabilization and result in inhibition of beta-catenin-mediated transcription...
- Disorders of sex development: new genes, new conceptsMakoto Ono
Molecular Genetics and Development Division, Prince Henry s Institute of Medical Research, Monash Medical Centre, Department of Anatomy and Biochemistry, Monash University, Clayton, Melbourne, Vic, Australia
Nat Rev Endocrinol 9:79-91. 2013..These advances are refining prognostic prediction and systematically improving the diagnosis and long-term management of children with DSDs...
- Acquisition of SOX transcription factor specificity through protein-protein interaction, modulation of Wnt signalling and post-translational modificationPascal Bernard
Prince Henry s Institute of Medical Research, Monash Medical Centre, PO Box 5152, Clayton, Melbourne, VIC 3168, Australia
Int J Biochem Cell Biol 42:400-10. 2010..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...
- SOX13 is up-regulated in the developing mouse neuroepithelium and identifies a sub-population of differentiating neuronsYi Wang
Human Molecular Genetics Laboratory, Prince Henry s Institute of Medical Research, 246 Clayton Road, Clayton, VIC 3168, Australia
Brain Res Dev Brain Res 157:201-8. 2005..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...
- Boys, girls and shuttling of SRY and SOX9Helena Sim
Human Molecular Genetics Laboratory, Prince Henry s Institute of Medical Research, Level 4 Block E, Monash Medical Centre, 246 Clayton Rd, Clayton, Melbourne, VIC 3168, Australia
Trends Endocrinol Metab 19:213-22. 2008..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...
- Wnt4 action in gonadal development and sex determinationPascal Bernard
Human Molecular Genetics Laboratory, Prince Henry s Institute of Medical Research, PO Box 5152, Clayton, VIC 3168, Australia
Int J Biochem Cell Biol 39:31-43. 2007..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...
- Sex determination: a 'window' of DAX1 activityLouisa M Ludbrook
Prince Henry s Institute of Medical Research, PO Box 5152, Clayton, VIC 3168, Australia
Trends Endocrinol Metab 15:116-21. 2004..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...
- Androgen receptor repeat length polymorphism associated with male-to-female transsexualismLauren Hare
Human Molecular Genetics Laboratory, Prince Henry s Institute of Medical Research, Melbourne, Australia
Biol Psychiatry 65:93-6. 2009..Specifically, we assessed the role of disease-associated repeat length polymorphisms in the androgen receptor (AR), estrogen receptor beta (ERbeta), and aromatase (CYP19) genes...
- The male fight-flight response: a result of SRY regulation of catecholamines?Joohyung Lee
Brain and Gender, Prince Henry s Institute of Medical Research, Monash Medical Centre, Melbourne, Australia
Bioessays 34:454-7. 2012..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...
- Dimerization of SOX9 is required for chondrogenesis, but not for sex determinationPascal Bernard
UCLA Department of Human Genetics, Gonda Center, Room 6357, 695 Charles Young Drive South, Los Angeles, CA 90095 7088, USA
Hum Mol Genet 12:1755-65. 2003..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...
- Comparative analysis of ATRX, a chromatin remodeling proteinDaniel J Park
Department of Zoology, The University of Melbourne, Gate 12 Royal Parade, Melbourne 3010, Australia
Gene 339:39-48. 2004..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...
- Characterisation of the marsupial-specific ATRY gene: implications for the evolution of male-specific functionDaniel J Park
Department of Zoology, The University of Melbourne, Melbourne VIC 3010, Australia
Gene 362:29-36. 2005..The conservation and loss of particular motifs identify those required for testicular function (ATRY) and function in other tissues (ATRX)...
- A familial missense mutation in the hinge region of DAX1 associated with late-onset AHC in a prepubertal femalePascal Bernard
Department of Human Genetics, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095 7088, USA
Mol Genet Metab 88:272-9. 2006..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...
- Paraspeckle protein p54nrb links Sox9-mediated transcription with RNA processing during chondrogenesis in miceKenji Hata
Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan
J Clin Invest 118:3098-108. 2008..These data suggest that p54nrb plays an important role in the regulation of Sox9 function and the formation of paraspeckle bodies during chondrogenesis...
- ATRX and sex differentiationPaisu Tang
Department of Zoology, The University of Melbourne, Victoria 3010, Australia
Trends Endocrinol Metab 15:339-44. 2004..We review what is known about ATRX as a chromatin remodeling protein, and its role in mammalian sex differentiation...
- Direct regulation of adult brain function by the male-specific factor SRYPhoebe Dewing
Department of Human Genetics, University of California, Los Angeles, Los Angles, California 90095, USA
Curr Biol 16:415-20. 2006..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 used to call them hermaphroditesEric Vilain
Department of Human Genetics, University of California Los Angeles School of Medicine, Los Angeles, California 90095 7088, USA
Genet Med 9:65-6. 2007
- Sex-specific expression of a novel gene Tmem184a during mouse testis differentiationTerje Svingen
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
Reproduction 133:983-9. 2007..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...