Lettieri, Antonella;
Oleari, Roberto;
van den Munkhof, Marleen Hester;
van Battum, Eljo Yvette;
Verhagen, Marieke Geerte;
Tacconi, Carlotta;
Spreafico, Marco;
... Cariboni, Anna; + view all
(2023)
SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability.
Nature Communications
, 14
(1)
, Article 8097. 10.1038/s41467-023-43820-z.
Preview |
Text
SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability.pdf - Published Version Download (17MB) | Preview |
Abstract
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.
| Type: | Article |
|---|---|
| Title: | SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-023-43820-z |
| Publisher version: | http://dx.doi.org/10.1038/s41467-023-43820-z |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, GROWTH-FACTOR, MURINE SEMAPHORIN, OLFACTORY SYSTEM, MIGRATION, BARRIER, PROTEINS, NRP1, PLASTICITY, DISRUPTS, FAMILY |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10188721 |
Archive Staff Only
 |
View Item |
