Biology subjects

Galichet, C.

Publications and source records attributed to Galichet, C..

5 recordsLinked to original sources

bioRxiv2024

Gonadotrophs have a dual origin, with most derived from pituitary stem cells during minipuberty.

Gonadotrophs are the essential pituitary endocrine cells for reproduction. They produce both luteinizing (LH) and follicle-stimulating (FSH) hormones that act on the gonads. Gonadotrophs first appear in the embryonic pituitary, along with other endocrine cell types, and all expand after birth. We show here that most gonadotrophs originate from a population of postnatal pituitary stem cells during minipuberty, while those generated in the embryo are maintained, revealing an unsuspected dual origin of the adult population. This has implications for our understanding of the establishment and regulation of reproductive functions, both in health and in disease.

developmental biology↗

bioRxiv2023

Sox3-null hypopituitarism depends on median eminence NG2-glia and is influenced by aspirin and gut microbiota

The median eminence (ME), located at the base of the hypothalamus, is an essential centre of information exchange between the brain and the pituitary. We and others previously showed that mutations and duplications affecting the transcription factor SOX3/Sox3 result in hypopituitarism, and this is likely of hypothalamic origin. We demonstrate here that the absence of Sox3 predominantly affects the ME with phenotypes that first occur in juvenile animals, despite the embryonic onset of SOX3 expression. In the pituitary, reduction in hormone levels correlates with a lack of endocrine cell maturation. In parallel, ME NG2-glia renewal and oligodendrocytic differentiation potential are affected. We further show that low-dose aspirin treatment, which is known to affect NG2-glia, or changes in gut microbiota, rescue both proliferative defects and hypopituitarism in Sox3 mutants. Our study highlights a central role of NG2-glia for ME function during a transitional period of post-natal development, and indicates their sensitivity to environmental signals.

neuroscience↗

bioRxiv2022

The identification of a gene expression signature of primordial follicle activation in mouse pregranulosa cells

Primordial follicles are quiescent ovarian structures comprised of a single oocyte surrounded by a layer of somatic supporting pregranulosa cells. Primordial follicle activation is the first step towards oocyte maturation and, ultimately, ovulation. As the number of quiescent primordial follicles is finite, their rate of activation is a critical parameter of the duration of the female reproductive lifespan. Activation status is established by the presence of cuboidal and proliferative granulosa cells in primary follicles, rather than squamous and quiescent pregranulosa cells in primordial follicles. Here, using a continuous Entropy Sort Feature Weighting approach on single-cell RNA sequencing data, we identify a distinct transcriptomic signature of activating pregranulosa cells in neonatal wildtype mice. This signature contains several genes previously linked with mature granulosa cells as well several novel candidates: Slc18a2, Tnni3, Fam13a and Myo1e. We confirm expression of Slc18a2 and TNNI3 in the granulosa cells of activating follicles in embryonic, neonatal and adult mouse ovaries. Perturbation of cell cycle inhibitor p27kip1 in Cdkn1b-/- mice results in complete activation of all primordial follicles during this neonatal period. Contrary to previous reports on this established mouse model, we find substantial transcriptomic changes in embryonic Cdkn1b-/- ovaries. Upon loss of cell-cycle inhibition, we find increased expression of our signature of pregranulosa cell activation, particularly that of cardiac troponin I (Tnni3). We conclude that pregranulosa cells engage a distinct transcriptional programme prior to cell-cycle dependent primordial follicle activation.

developmental biology↗

bioRxiv2020

Dentate gyrus development requires a cortical hem-derived astrocytic scaffold.

During embryonic development, radial glial cells give rise to neurons, then to astrocytes following the gliogenic switch. Timely regulation of the switch, operated by several transcription factors, is fundamental for allowing coordinated interactions between neurons and glia. We deleted the gene for one such factor, SOX9, early during mouse brain development and observed a significantly compromised dentate gyrus (DG). We dissected the origin of the defect, targeting embryonic Sox9 deletion to either the DG neuronal progenitor domain or the adjacent cortical hem (CH). We identified in the latter previously uncharacterized ALDH1L1+ astrocytic progenitors, which form a fimbrial-specific glial scaffold necessary for neuronal progenitor migration towards the developing DG. Our results highlight an early crucial role of SOX9 for DG development through regulation of astroglial potential acquisition in the CH. Moreover, we illustrate how formation of a local network, amidst astrocytic and neuronal progenitors originating from adjacent domains, underlays brain morphogenesis.

developmental biology↗

bioRxiv2020

SOX2 is required independently in both stem and differentiated cells for pituitary tumour genesis in p27 null mice.

Loss of P27 predominantly results in development of murine pituitary intermediate lobe (IL) tumours. We previously showed that the pleiotropic protein P27 can drive repression of the transcription factor Sox2. This interaction plays an important role during development of p27-/- IL tumours because loss of one copy of Sox2 diminishes tumorigenesis. Here, we have explored the cellular origin and mechanisms underlying melanotroph tumorigenesis in p27-/- IL. We show that IL hyperplasia is associated with reduced cellular differentiation, while levels of SOX2 increase in both stem cells (SC) and melanotrophs. Using loss-of-function and lineage tracing approaches, we demonstrate that SOX2 is required cell-autonomously in p27-/- melanotrophs and SCs for tumorigenesis. This is supported by studies deleting the Sox2 regulatory region 2 (Srr2), which is the target of P27 repressive action. Single cell transcriptomic analysis reveals that activation of a SOX2-dependent MAPK pathway in SCs is important for p27-/- tumorigenesis. Our data highlight different roles of SOX2 following loss of p27, according to the cellular context. Furthermore, we uncover a tumor-promoting function for SCs, which is SOX2-dependant. In conclusion, our results imply that targeting SCs, in addition to tumour cells themselves, may represent an efficient anti-tumoral strategy in certain contexts.

cancer biology↗