Hypopituitarism in Sox3 null mutants correlates with altered NG2-glia in the median eminence 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 l...

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Veröffentlicht in:PLoS genetics 2024-09, Vol.20 (9), p.e1011395
Hauptverfasser: Galichet, Christophe, Rizzoti, Karine, Lovell-Badge, Robin
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Rizzoti, Karine
Lovell-Badge, Robin
description 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 extrinsic signals.
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subjects Analysis
Animals
Aspirin
Aspirin - pharmacology
Biology and Life Sciences
Cell Differentiation
Dosage and administration
Gastrointestinal Microbiome - genetics
Hypopituitarism
Hypopituitarism - genetics
Identification and classification
Male
Median Eminence - metabolism
Medicine and Health Sciences
Mice
Mice, Knockout
Microbiota (Symbiotic organisms)
Neuroglia
Neuroglia - metabolism
Pituitary Gland - metabolism
Research and Analysis Methods
SOXB1 Transcription Factors - genetics
SOXB1 Transcription Factors - metabolism
Transcription factors
title Hypopituitarism in Sox3 null mutants correlates with altered NG2-glia in the median eminence and is influenced by aspirin and gut microbiota
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