A5033838168- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sexual Differentiation and Disorders
- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Animal Genetics and Reproduction
- Chromosomal and Genetic Variations
- Renal and related cancers
- Wnt/β-catenin signaling in development and cancer
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Urological Disorders and Treatments
- Retinal Development and Disorders
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- Insect Resistance and Genetics
- Plant Virus Research Studies
- Developmental Biology and Gene Regulation
- Kruppel-like factors research
- Sex and Gender in Healthcare
- Genetics and Physical Performance
- Estrogen and related hormone effects
- Renal cell carcinoma treatment
- Cancer-related gene regulation
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
Université Côte d'Azur
2016-2025
Inserm
2016-2025
Institut de Biologie Valrose
2015-2025
Centre National de la Recherche Scientifique
2015-2024
Observatoire de la Côte d’Azur
2022
École Normale Supérieure
2009-2012
Weatherford College
2010
Dana-Farber Cancer Institute
2004
University of Pennsylvania
2004
Centre for Life
2002
To examine whether the transcription factor Sox9 has an essential role during sequential steps of chondrocyte differentiation, we have used Cre/loxP recombination system to generate mouse embryos in which either is missing from undifferentiated mesenchymal cells limb buds or gene inactivated after chondrogenic condensations. Inactivation before condensations resulted a complete absence both cartilage and bone, but markers for different axes development showed normal pattern expression....
The mechanism that causes neural stem cells in the central nervous system to switch from neurogenesis gliogenesis is poorly understood. Here we analyzed spinal cord development of mice which transcription factor Sox9 was specifically ablated by CRE/loxP recombination system. These exhibit defects specification oligodendrocytes and astrocytes, two main types glial Accompanying an early dramatic reduction progenitors myelin-forming oligodendrocytes, there a transient increase motoneurons....
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-...
Sex determination in mammals directs an initially bipotential gonad to differentiate into either a testis or ovary. This decision is triggered by the expression of sex-determining gene Sry, which leads activation male-specific genes including HMG-box containing Sox9. From transgenic studies mice it clear that Sox9 sufficient induce formation. However, there no direct confirmation for essential role determination. The presented here are first experimental proof mediating switch from ovarian...
The sex of an individual is determined by the fate gonad. While expression Sry and Sox9 sufficient to induce male development, we here show that female differentiation requires activation canonical beta-catenin signaling pathway. controlled Rspo1 in XX gonads knockout mice masculinized gonads. Molecular analyses demonstrate absence female-specific Wnt4 as a consequence XY-like vascularization steroidogenesis. Moreover, germ cells embryos changes cellular adhesions failure enter specific...
Sex determination is a unique process that allows the study of multipotent progenitors and their acquisition sex-specific fates during differentiation gonad into testis or an ovary. Using time series single-cell RNA sequencing (scRNA-seq) on ovarian Nr5a1-GFP+ somatic cells sex determination, we identified single population early giving rise to both pre-granulosa potential steroidogenic precursor cells. By comparing XX XY cells, provide evidence gonadal supporting are specified from these by...
Epithelial–mesenchymal transformation is a critical developmental process reiterated in multiple organs throughout embryogenesis. Formation of endocardial cushions, primordia valves and septa, classic example epithelial–mesenchymal transformation. Several gene mutations are known to affect cardiac valve formation. Sox9 activated when endothelial cells undergo mesenchymal migrate into an extracellular matrix, called jelly, form cushions. In -null mutants, cushions markedly hypoplastic. these...
Abstract It is widely accepted that the process of retinal cell fate determination under tight transcriptional control mediated by a combinatorial code transcription factors. However, exact repertoire factors necessary for genesis each type remains to be fully defined. Here we show HMG‐box factor, Sox9, expressed in multipotent mouse progenitor cells throughout retinogenesis. We also find Sox9 downregulated differentiating neuronal populations, yet expression Müller glial persists into...
Congenital abnormalities of the kidney and urinary tract are some most common defects detected in unborn child. Kidney growth is controlled by GDNF/RET signalling pathway, but molecular events required for activation RET downstream targets still poorly understood. Here we show that SOX9, a gene involved campomelic dysplasia (CD) humans, together with its close homologue SOX8, plays an essential role signalling. Expression SOX9 can be found from earliest stages renal development within...
Differentiation of germ cells into male gonocytes or female oocytes is a central event in sexual reproduction. Proliferation and differentiation fetal depend on the sex embryo. In mouse embryos, cell proliferation regulated by RNA helicase Mouse Vasa homolog gene factors synthesized somatic Sertoli promote gonocyte differentiation. female, ovarian requires activation WNT/β-catenin signaling pathway secreted protein RSPO1. Using models, we now show that Rspo1 also activates cells. XX Rspo1−/−...
Gonadal sex determination represents a unique model for studying cell fate decisions. However, complete understanding of the different lineages forming developing testis and ovary remains elusive. Here, we investigated origin, specification, subsequent sex-specific differentiation previously uncharacterized population supporting-like cells (SLCs) in mouse gonads. The SLC lineage is closely related to coelomic epithelium specified as early E10.5, making it first somatic be bipotential gonad....
Abstract Despite the importance of germ cell (GC) differentiation for sexual reproduction, gene networks underlying their fate remain unclear. Here, we comprehensively characterize expression dynamics during sex determination based on single‐cell RNA sequencing 14 914 XX and XY mouse GCs between embryonic days (E) 9.0 16.5. We found that diverge transcriptionally as early E11.5 with upregulation genes downstream bone morphogenic protein (BMP) nodal/Activin pathways in GCs, respectively. also...
Sex determination in mammals depends on the differentiation of supporting lineage gonads into Sertoli or pregranulosa cells that govern testis and ovary development, respectively. Although Y-linked testis-determining gene Sry has been identified, ovarian-determining factor remains unknown. In this study, we identified -KTS, a major, alternatively spliced isoform Wilms tumor suppressor WT1, as key determinant female sex determination. Loss -KTS variants blocked gonadal mice, whereas increased...
Male genital development in XY mammalian fetuses is triggered by the action of hormones, including testosterone, secreted developing testes. Defects this process are a cause for Differences Sex Development (DSD), one most common congenital abnormalities humans. Fetal Leydig Cells (FLC) play central role synthesis masculinizing hormones Yet, genetic cascade controlling their differentiation poorly understood. Here we investigate orphan nuclear receptor NR2F2 (COUP-TFII) FLC development. We...
The gonad arises from the thickening of coelomic epithelium and then commits into sex determination process. Testis differentiation is activated by expression Y-linked gene Sry, which promotes cell proliferation Sertoli cells, supporting cells testis. In absence Sry (XX individuals), activation WNT/CTNNB1 signalling, via upregulation Rspo1 Wnt4, ovarian differentiation. However, Wnt4 are expressed in early undifferentiated both sexes, Axin2-lacZ, a reporter canonical region E11.5 gonadal...
In mammals, male sex determination is governed by SRY-dependent activation of Sox9, whereas female development involves R-spondin1 (RSPO1), an activator the WNT/beta-catenin signaling pathway. Genetic analyses in mice have demonstrated Sry and Sox9 to be both required sufficient induce testicular development. These genes are therefore considered as master regulators Indeed, female-to-male reversal XX Rspo1 mutant correlates with expression, suggesting that this transcription factor induces...