A5022075579- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sexual Differentiation and Disorders
- Sperm and Testicular Function
- Urological Disorders and Treatments
- Animal Genetics and Reproduction
- Reproductive Biology and Fertility
- Epigenetics and DNA Methylation
- Testicular diseases and treatments
- Renal and related cancers
- Chromosomal and Genetic Variations
- Congenital heart defects research
- Genetics and Neurodevelopmental Disorders
- Developmental Biology and Gene Regulation
- Cell Adhesion Molecules Research
- Urologic and reproductive health conditions
- Cancer-related molecular mechanisms research
- Sexuality, Behavior, and Technology
- RNA Research and Splicing
- Reproductive System and Pregnancy
- Cancer Research and Treatments
- Protein Hydrolysis and Bioactive Peptides
- Fibroblast Growth Factor Research
- Infant Nutrition and Health
- Hedgehog Signaling Pathway Studies
- Gender Studies in Language
Hudson Institute of Medical Research
2015-2024
Hudson Institute
2024
Monash University
2011-2024
Monash Medical Centre
2007-2023
The University of Melbourne
2017-2020
Monash Institute of Medical Research
2007-2013
St Vincents Institute of Medical Research
2012
Institute for Medical Research
2008-2012
Australian Regenerative Medicine Institute
2012
University of Freiburg
2001-2008
In the presence of Y-chromosomal gene Sry, bipotential mouse gonads develop as testes rather than ovaries. The autosomal Sox9, a likely and possibly direct Sry target, can induce testis development in absence Sry. Sox9 is thus sufficient but not necessarily essential for induction. Mutational inactivation one allele SOX9/Sox9 causes sex reversal humans mice. Because Sox9(-/-) embryos die around Embryonic Day 11.5 (E11.5) at onset testicular morphogenesis, differentiation mutant XY gonad be...
MicroRNAs are important regulators of developmental gene expression, but their contribution to fetal gonad development is not well understood. We have identified the evolutionarily conserved gonadal microRNAs miR-202-5p and miR-202-3p as having a potential role in regulating mouse embryonic differentiation. These expressed sexually dimorphic pattern primordial XY differentiates into testis, with strong expression Sertoli cells. In vivo, ectopic pri-miR-202 XX gonads did result molecular...
In mammalian embryonic gonads, SOX9 is required for the determination of Sertoli cells that orchestrate testis morphogenesis. To identify genetic networks directly regulated by SOX9, we combined analysis SOX9-bound chromatin regions from murine and bovine foetal testes with sequencing RNA samples mouse lacking Sox9. We found controls a conserved programme involves most sex-determining genes. testes, modulates both transcription or indirectly sex-specific differential splicing its target...
Sex determination in fetal germ cells depends on a balance between exposure to retinoic acid (RA) and the degradation of RA achieved by testis-specific expression catabolic cytochrome P450 enzyme, CYP26B1. Therefore, identification factors regulating Cyp26b1 gene is an important goal reproductive biology. We used situ hybridization demonstrate that transcription factor genes steroidogenic factor-1 (Sf1) Sry-related HMG box 9 (Sox9) are coexpressed Sertoli cells, whereas Sf1 Leydig mouse...
Human DAX1 duplications cause dosage-sensitive sex reversal (DSS) whereby chromosomally XY individuals can develop as females due to gonadal dysgenesis. However, the mechanism of DSS-adrenal hypoplasia congenita on X, gene 1 (DAX1) action in fetal testis is unknown. We show that testes from Dax1-overexpressing transgenic mice, expression key testis-promoting sex-determining region Y (SRY)-box-9 (Sox9) reduced. Moreover, Sox9 heterozygotes, which development usually normal, Dax1...
Background In human embryogenesis, loss of SRY (sex determining region on Y), SOX9 (SRY-related HMG box 9) or SF1 (steroidogenic factor 1) function causes disorders sex development (DSD). A defining event vertebrate determination is male-specific upregulation and maintenance expression in gonadal pre-Sertoli cells, which preceded by transient mammals. mice, Sox9 regulation under the transcriptional control SRY, via a conserved testis-specific enhancer (TES). Regulation however poorly...
X-linked ATR-X (alpha thalassemia, mental retardation, X-linked) syndrome in males is characterized by facial dysmorphism, alpha thalassemia and urogenital abnormalities, including small testes. It unclear how mutations the chromatin-remodeling protein ATRX cause these highly specific clinical features, since widely expressed during organ development. To investigate mechanisms underlying testicular defects observed syndrome, we generated ScAtrxKO (Sertoli cell Atrx knockout) mice with...
Patients with 46,XY gonadal dysgenesis (GD) exhibit genital anomalies, which range from hypospadias to complete male-to-female sex reversal. However, a molecular diagnosis is made in only 30% of cases. Heterozygous mutations the human FGFR2 gene cause various craniosynostosis syndromes including Crouzon and Pfeiffer, but testicular defects were not reported. Here, we describe patient whose features would suggest represent new FGFR2-related syndrome, XY reversal or CSR. The was chromosomally...
Male sex determination in mammals relies on determining region Y–mediated upregulation of region–box 9 (SOX9) expression XY gonads, whereas Wnt family member (WNT)/R-spondin 1 signaling and forkhead box L2 (FOXL2) drive female XX gonads. Fibroblast growth factor (FGF) ensures sustained SOX9 through repression one the ovarian pathways (WNT signaling), significance FGF-mediated FOXL2 pathway has not been studied. Previously, we demonstrated that FGFR2 is receptor for FGF9 gonad. Whether a...
Abstract Balanced production and degradation of retinoids is important in regulating development several organ systems the vertebrate embryo. Among these, it known that retinoic acid (RA), retinoid‐catabolyzing enzyme CYP26B1 together regulate sex‐specific behavior germ cells developing mouse gonads. We report here gene encoding a cytosolic class‐1 aldehyde dehydrogenase, ALDH1A1, weak catalyst RA production, strongly expressed male‐specific manner somatic testis, beginning shortly after Sry...
During mouse sex determination, SRY upregulates the core testis-specific enhancer of <i>Sox9</i>, TESCO. Mutations in human <i>SRY</i> are found one third cases with XY pure gonadal dysgenesis (XY GD; Swyer syndrome), while two thirds remain unexplained. Heterozygous <i>SOX9</i> mutations can cause GD association skeletal malformation syndrome campomelic dysplasia. We hypothesized that TESCO could isolated GD. Sixty-six an intact were analyzed for point or...
Women and other mammalian females are born with a finite supply of oocytes that determine their reproductive lifespan. During fetal development, individual enclosed by protective layer granulosa cells to form primordial follicles will grow, mature, eventually release the oocyte for potential fertilization. Despite knowledge dysfunctional die without cell-oocyte interactions, mechanisms which these establish communication is unknown. We previously identified two members Iroquois homeobox...
Structured Abstract Objective To investigate the role of a potential SOX9 target gene, Tyro3 , along with its family members, Axl and Mertk (TAM family) in mouse testis development. Design Experimental laboratory study. Setting Research institute units. Subject(s) Embryonic day (E)11.5 Swiss gonads for ex vivo gonad culture; knockout embryos. Intervention(s) E11.5 were cultured hanging droplets 30 µL DMEM medium supplemented 10% FBS 1% antibiotic-antimycotic. A pair treated 20 μM BMS-777607...
Background Mice harbouring gene mutations that cause phenotypic abnormalities during organogenesis are invaluable tools for linking function to normal development and human disorders. To generate mouse models novel alleles involved in we conducted a phenotype-driven, genome-wide mutagenesis screen mice using the mutagen N-ethyl-N-nitrosourea (ENU). Methodology/Principal Findings ENU was injected into male C57BL/6 transmitted through germ-line. ENU-induced were bred homozygosity G3 embryos...