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MAYERE, C.

Publications and source records attributed to MAYERE, C..

3 recordsLinked to original sources

An ancestral pronephric contribution reveals the multilineage origin of the teleost gonad and revises the evolution of vertebrate gonadogenesis

Challenging the paradigm that pronephric field contribution to gonadal formation would be an amniote innovation, we demonstrate this trait is ancestral to bony vertebrates. Using cell lineage tracing, single-cell and spatial transcriptomics, and functional validation, we show that the teleost gonad arises from three distinct embryonic tissues, the pronephros, the coelomic epithelium, and the lateral plate mesoderm, in contrast to amniotes. This multi-tissue origin generates an unexpected lineage-based cellular diversity. Further cross-species comparisons over medaka, mouse, chicken and turtle unravel how lineage-specific deviations shape early gonadal development. Specifically, we map these variations amongst the different gene regulatory networks, outlining their physiological implications for specialized gonadal functions. Our results support a model in which heterochronic shifts are coupled to regulatory rewiring of conserved gene networks, driving lineage-specific developmental trajectories through a canalized developmental system drift.

developmental biology↗

Ovarian development is driven by early spatiotemporal priming of the coelomic epithelium

Ovarian organogenesis relies on the coordinated specification of supporting and steroidogenic lineages from multipotent coelomic epithelium (CE) progenitors. However, it remains unclear how ovarian cellular diversity arises and whether CE progenitors are fate-biased before or after ingression into the gonad. We show that CE cells in fetal mouse and human ovaries are transcriptionally heterogeneous and spatially organized into subdomains already primed toward supporting or steroidogenic identities. CE priming is dynamic, influenced by proximity to the mesonephros, with a transient coexistence of both progenitor types before resolution toward a predominantly supporting-biased CE. In mice, delamination of primed CE cells seeds intragonadal niches that generate pre-granulosa and steroidogenic progenitors. We further demonstrate that fetal steroidogenic progenitors give rise to adult stromal and theca cells, and that granulosa cells have a dual origin from CE-derived and supporting-like cells. Together, these findings reveal a conserved, spatially encoded program of ovarian lineage specification.

developmental biology↗

Loss of NR5A1 in Sertoli cells after sex determination changes their cellular identity and induces their death by anoikis

NR5A1 is an orphan nuclear receptor crucial for gonadal development in mammals. In the mouse testis it is expressed both in Sertoli cells (SC) and Leydig cells (LC). To investigate its role posteriorly to sex determination, we have generated and analysed mice lacking NR5A1 in SC from embryonic day (E) 13.5 onwards (Nr5a1SC-/- mutants). Ablation of Nr5a1 impairs the expression of genes characteristic of SC identity (e.g., Sox9, Amh), makes SC to progressively die from E14.5 by a Trp53-independent mechanism, and induces disorganization of the testis cords, which, together, yields germ cells (GC) to prematurely enter meiosis and die, instead of becoming quiescent. Single-cell RNA-sequencing experiments revealed that Nr5a1-deficient SC acquire a pre-granulosa cell-like identity, and profoundly modify the landscape of the adhesion molecules and extracellular matrix they express. We propose therefore that SC lacking NR5A1 transdifferentiate and die by anoikis. Fetal LC do not display major changes in their transcriptome, indicating that SC are not required beyond E14.5 for their emergence or maintenance. In contrast, adult LC were missing in Nr5a1SC-/- postnatal testes. In addition, adult males display Mullerian duct derivatives (i.e., uterus, vagina), as well as a decreased anogenital distance and a shorter penis that can be explained by loss of AMH production and defective HSD17B1- and HSD17B3-mediated synthesis of testosterone in SC during fetal life. Together, our findings indicate that Nr5a1 expressed in SC after the period of sex determination safeguards SC identity, which maintains proper seminiferous cord organization and prevents GC to enter meiosis.

developmental biology↗