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 thia-cal horse supplement 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 hbl5266ca 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.