دورية أكاديمية
أعرض في EDS

SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability.

التفاصيل البيبلوغرافية
العنوان: SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability.
المؤلفون: Lettieri A; Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy.; Department of Health Sciences, University of Milan, Via di Rudinì 8, 20142, Milano, Italy., Oleari R; Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy., van den Munkhof MH; Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands., van Battum EY; Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands., Verhagen MG; Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.; VIB-KU Leuven, Center for Brain & Disease Research, Leuven, Belgium., Tacconi C; Department of Biosciences, University of Milan, Via Celoria 26, 20133, Milan, Italy.; Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy., Spreafico M; Department of Biosciences, University of Milan, Via Celoria 26, 20133, Milan, Italy., Paganoni AJJ; Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy., Azzarelli R; Wellcome - Medical Research Council Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, UK., Andre' V; Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy., Amoruso F; Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy., Palazzolo L; Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy., Eberini I; Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy., Dunkel L; Centre for Endocrinology William Harvey Research Institute Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK., Howard SR; Centre for Endocrinology William Harvey Research Institute Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.; Department of Paediatric Endocrinology, Barts Health NHS Trust, London, E1 1FR, UK., Fantin A; Department of Biosciences, University of Milan, Via Celoria 26, 20133, Milan, Italy. alessandro.fantin@unimi.it., Pasterkamp RJ; Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands. r.j.pasterkamp@umcutrecht.nl., Cariboni A; Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. anna.cariboni@unimi.it.
المصدر: Nature communications [Nat Commun] 2023 Dec 07; Vol. 14 (1), pp. 8097. Date of Electronic Publication: 2023 Dec 07.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Gonadotropin-Releasing Hormone*/metabolism , Semaphorins*/genetics , Semaphorins*/metabolism, Humans ; Median Eminence/metabolism ; Capillary Permeability ; Neurons/metabolism ; Puberty
مستخلص: Innervation of the hypothalamic median eminence by Gonadotropin-Releasing Hormone (GnRH) neurons is vital to ensure puberty onset and successful reproduction. However, the molecular and cellular mechanisms underlying median eminence development and pubertal timing are incompletely understood. Here we show that Semaphorin-6A is strongly expressed by median eminence-resident oligodendrocytes positioned adjacent to GnRH neuron projections and fenestrated capillaries, and that Semaphorin-6A is required for GnRH neuron innervation and puberty onset. In vitro and in vivo experiments reveal an unexpected function for Semaphorin-6A, via its receptor Plexin-A2, in the control of median eminence vascular permeability to maintain neuroendocrine homeostasis. To support the significance of these findings in humans, we identify patients with delayed puberty carrying a novel pathogenic variant of SEMA6A. In all, our data reveal a role for Semaphorin-6A in regulating GnRH neuron patterning by tuning the median eminence vascular barrier and thereby controlling puberty onset.
(© 2023. The Author(s).)
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust
المشرفين على المادة: 33515-09-2 (Gonadotropin-Releasing Hormone)
0 (Semaphorins)
0 (SEMA6A protein, human)
تواريخ الأحداث: Date Created: 20231207 Date Completed: 20231216 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10703890
DOI: 10.1038/s41467-023-43820-z
PMID: 38062045
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-023-43820-z