A5006014020- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sexual Differentiation and Disorders
- Sperm and Testicular Function
- Animal Genetics and Reproduction
- Genomics and Chromatin Dynamics
- Reproductive System and Pregnancy
- Chromosomal and Genetic Variations
- Estrogen and related hormone effects
- Renal and related cancers
- Ubiquitin and proteasome pathways
- Reproductive Biology and Fertility
- Endometriosis Research and Treatment
- Demographic Trends and Gender Preferences
- Effects and risks of endocrine disrupting chemicals
- Wnt/β-catenin signaling in development and cancer
- RNA regulation and disease
- Peptidase Inhibition and Analysis
- Reproductive Physiology in Livestock
- Neuroscience and Neuropharmacology Research
- Congenital heart defects research
- Photosynthetic Processes and Mechanisms
- Ion channel regulation and function
- Testicular diseases and treatments
- Inflammatory mediators and NSAID effects
- Cancer-related molecular mechanisms research
Institut de Génétique Humaine
2014-2024
Université de Montpellier
2011-2024
Centre National de la Recherche Scientifique
2011-2024
Monash University
2018
Department of Embryology
2008
Inserm
1991-2006
Université de Rennes
2005
Centre de Recherche en Biologie cellulaire de Montpellier
1992-2005
Massachusetts General Hospital
2002
University of Freiburg
2000
For proper male sexual differentiation, anti-Müllerian hormone (AMH) must be tightly regulated during embryonic development to promote regression of the Müllerian duct. However, molecular mechanisms specifying onset AMH in mammals are not yet clearly defined. A DNA-binding element for steroidogenic factor 1 (SF-1), a member orphan nuclear receptor family, located proximal promoter has recently been characterized and demonstrated as being essential gene activation. requirement specific...
The genes encoding members of the wingless-related MMTV integration site (WNT) and fibroblast growth factor (FGF) families coordinate growth, morphogenesis, differentiation in many fields cells during development. In mouse, Fgf9 Wnt4 are expressed gonads both sexes prior to sex determination. Loss leads XY reversal, whereas loss results partial testis development XX gonads. However, relationship between these signals male sex-determining gene, Sry, was unknown. We show through gain-...
Cell fate decisions require appropriate regulation of key genes.
Activation by the Y-encoded testis determining factor SRY and maintenance of expression Sox9 gene encoding central transcription Sertoli cell differentiation are key events in mammalian sexual program. In mouse XY gonad, SOX9 upregulates Fgf9, which initiates a Sox9/Fgf9 feedforward loop, is stimulated prostaglandin D2 (PGD2) producing lipocalin D synthase (L-PGDS, or PTDGS) enzyme, accelerates commitment to male pathway. an attempt decipher genetic relationships between L-Pgds/PGD2 pathway...
Cell lineages of the early human gonad commit to one two mutually antagonistic organogenetic fates, testis or ovary. Some individuals with a 46,XX karyotype develop testes ovotestes (testicular ovotesticular disorder sex development; TDSD/OTDSD), due presence testis-determining gene, SRY Other rare complex syndromic forms TDSD/OTDSD are associated mutations in pro-ovarian genes that repress development (e.g. WNT4); however, genetic cause more common non-syndromic is unknown. Steroidogenic...
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...
Many transcription factors have been identified and implicated in male sex determination pathway. Specifically involved Sertoli cell differentiation subsequent anti-Müllerian hormone (AMH) secretion eutherian mammals, they include steroidogenic factor-1 (SF-1), SOX9 (SRY HMG box related gene 9), WT1 (Wilms' tumor 1), GATA-4 (a zinc finger factor). These described to execute their function the pathway by controlling AMH transcriptional expression. To understand hierarchies of these...
The human Y-linked testis determining gene <i>SRY</i> encodes a protein with DNA binding domain from the high mobility group box family. To date, no function has been assigned to amino acid sequences located outside this motif. Here, we identify in yeast two-hybrid screen PDZ termed SIP-1, as an interacting SRY. <i>In vitro</i>, biochemical analysis, immunoprecipitation experiments, well expression of SIP-1 embryonic confirm that two proteins can interact together. Interacting domains were...
In mammals, male sex determination starts when the Y chromosome Sry gene is expressed within undetermined gonad. One of earliest effect expression to induce up-regulation Sox9 in developing SOX9, like SRY, contains a high mobility group domain and sufficient testis differentiation transgenic XX mice. Before sexual differentiation, SOX9 protein initially found cytoplasm undifferentiated gonads from both sexes. At time anti-Müllerian hormone expression, it becomes localized nuclear compartment...
The Rho family of GTP-binding proteins plays critical roles during myogenesis induction. To elucidate their role later myogenesis, we have analyzed RhoA function myoblast fusion into myotubes. We find that activity is rapidly and transiently increased when cells are shifted differentiation medium then decreased until fusion. must be down-regulated to allow fusion, because expression a constitutively active form (RhoAV14) inhibits this process. RhoAV14 perturbs the localization M-cadherin,...
We have studied the expression of human SRY protein (termed p27SRY) in two different cell lines by using specific antibodies. Confocal microscopy enabled us to localize p27SRY precisely nucleus a discrete punctuate pattern. Furthermore, through microinjection experiments, we demonstrated that localization into was an event involving NH2-terminal part high mobility group (HMG) domain. With help several synthetic peptides and various mutants, characterized bipartite basic motif this...
The effects of a novel glutamate analogue, (trans)-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD), have been tested in striatal neurons primary culture and Xenopus oocytes injected with rat brain RNA. Both systems previously shown to contain well characterized metabotropic receptors coupled phospholipase C (Qp), as ionotropic receptors. In neurons, ACPD stimulated inositol phosphate (InsP) accumulation (EC50 = 9.7 +/- 2.5 microM; maximal effect, 184.7 11.6% basal accumulation). This effect was...
Abstract Gonadal sexual fate in mammals is determined during embryonic development and must be actively maintained adulthood. In the mouse ovary, oestrogen receptors FOXL2 protect ovarian granulosa cells from transdifferentiation into Sertoli cells, their testicular counterpart. However, mechanism underlying protective effect unknown. Here, we show that TRIM28 required to prevent female-to-male sex reversal of ovary after birth. We found upon loss Trim28 , transdifferentiate through an...
Of the several strategies that eukaryotes have evolved to modulate transcription factor activity, phosphorylation is regarded as one of major mechanisms in signal-dependent transcriptional control. To conclusively demonstrate human sex-determining gene SRY affected by such a post-translational control mechanism, we analyzed its status living cells. In present study, show cyclic AMP-dependent protein kinase (PKA) phosphorylates vitro well vivo on serine residues located N-terminal part...
Through intercellular signalling, the somatic compartment of foetal testis is able to program primordial germ cells undergo spermatogenesis. Fibroblast growth factor 9 and several members transforming β superfamily are involved in this process testis, counteracting induction meiosis by retinoic acid activating germinal mitotic arrest. Here, using vitro vivo approaches, we show that prostaglandin D2 (PGD2), which produced through both L-Pgds H-Pgds enzymatic activities cell compartments plays...
Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesic drugs, such as acetaminophen (APAP), are frequently taken during pregnancy, even in combination. However, they can favour genital malformations newborn boys reproductive disorders adults. Conversely, the consequences on postnatal ovarian development female health after utero exposure unknown. Here, we found that mice, to therapeutic doses of APAP-ibuprofen combination sex determination led delayed meiosis entry progression...
Male development in mammals depends on the activity of two SOX gene: Sry and Sox9, embryonic testis. As deletion Enhancer 13 (Enh13) Sox9 gene results XY male-to-female sex reversal, we explored critical elements necessary for its function hence, testis male development. Here, demonstrate that while microdeletions individual transcription factor binding sites (TFBS) Enh13 lead to normal testicular development, combined just SRY/SOX motifs can alone fully abolish leading reversal. This...
Anti-müllerian hormone type II receptor (AMHRII) is a serine/threonine and member of receptors the transforming growth factor beta superfamily. AMHRII has been recently identified in humans, mice, rats, rabbits. In male embryo, gene shown to be expressed Sertoli's cells, Leydig's cells mesenchymal surrounding müllerian duct. To determine functional region promoter as well factors controlling expression, we used 1.1-kilobase DNA fragment from 5'-flanking human generate series deletion or...