Oleari, R;
Caramello, A;
Campinoti, S;
Lettieri, A;
Ioannou, E;
Paganoni, A;
Fantin, A;
... Ruhrberg, C; + view all
(2019)
Plxna1 and Plxna3 cooperate to pattern the nasal axons that guide gonadotropin-releasing hormone neurons.
Development
, 146
, Article dev176461. 10.1242/dev.176461.
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Abstract
The gonadotropin releasing hormone (GnRH) neurons regulate puberty onset and sexual reproduction by secreting GnRH to activate and maintain the hypothalamic-pituitary gonadal axis. During embryonic development, GnRH neurons migrate along olfactory and vomeronasal axons through the nose into the brain, where they project to the median eminence to release GnRH. The secreted glycoprotein SEMA3A binds its receptors neuropilin (NRP) 1 or NRP2 to position these axons for correct GnRH neuron migration, with an additional role for the NRP co-receptor PLXNA1. Accordingly, mutations in SEMA3A, NRP1, NRP2 and PLXNA1 have been linked to defective GnRH neuron development in mice and inherited GnRH deficiency in humans. Here, we show that only the combined loss of PLXNA1 and PLXNA3 phenocopied the full spectrum of nasal axon and GnRH neuron defects of SEMA3A knockout mice. Together with Plxna1, the human ortholog of Plxna3 should therefore be investigated as a candidate gene for inherited GnRH deficiency.
| Type: | Article |
|---|---|
| Title: | Plxna1 and Plxna3 cooperate to pattern the nasal axons that guide gonadotropin-releasing hormone neurons |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1242/dev.176461 |
| Publisher version: | https://doi.org/10.1242/dev.176461 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | GnRH neuron, olfactory bulb, testes, axon guidance, plexin, semaphorin, hypogonadotropic hypogonadism, Kallmann Syndrome |
| 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 Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10083182 |
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