Aim: 

Gonadotropin-releasing hormone (GnRH)-neurons are hypothalamic neuroendocrine cells controlling the physiology of reproduction. During development, GnRH-neurons originate in the nose and migrate into the hypothalamus, following olfactory nerves. During this journey, many signals participate to orchestrate the proper migration of GnRH-neurons and targeting of olfactory axons. We have recently shown that two different classes of Neuropilins (Nrp)-binding molecules affect the chemomigration of immortalised GnRH-neurons: semaphorins 3A/3F and Vascular Endothelial Growth Factor (VEGF).

Methods: 

Here, using different experimental approaches and taking advantage of knockout (KO) mice for semaphorins/VEGF signalling-pathways we investigated their roles in GnRH/olfactory systems. Using RT-PCR, we showed that isolated GFP-GnRH-neurons express Nrp-1, Nrp-2 (Cariboni et al., 2007), VEGF and Flt-1 (a VEGF receptor acting with Nrp to transduce intracellular signal).

Results: 

The analysis of Nrp-1 and VEGF KO mice showed a reduction in the total number of GnRH-neurons, suggesting a role of VEGF in the survival of these cells. No differences in number and positioning of GnRH-neurons were found in Flt-1 KO mice. However, in the Nrp-2/Nrp-1 double KO mice, an aberrant migration of GnRH-neurons was observed, accompanied by disruption of olfactory axons.

Conclusion: 

These data suggest multiple roles of Nrps and their ligands in the survival and migration of GnRH-neurons as well as in the positioning of olfactory