FURTHER EVIDENCES ON THE ACTION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) ON DEVELOPING GnRH NEURONS

Gonadotropin-releasing hormone (GnRH) neurons, play an essential role in reproductive functions. These neurons originate in the olfactory region and during development they migrate into the hypothalamus. In humans, defects of GnRH neuron migration results in delayed or absent pubertal maturation and infertility. We have reported recently that vascular endothelial growth factors (VEGF) may plays a relevant role in the migration process (Cariboni et al, in preparation). VEGF is a major regulator of vasculogenesis by interaction with Flt-1 and Flk-1 TK receptors. In this study, the provide further evidence to confirm interactions between VEGF, blood vessels and the GnRH. We first show that in mice during the appearance and migration of GnRH neurons there is a network of blood vessels around the olfactory placode, the vomeronasal organ, and in the nasal mesenchyme. By RT-PCR and VEGF-LacZ reporter mice, we found that VEGF is abundantly expressed in the developing olfactory structures; moreover, in FACS-isolated embryonic GFP-GnRH neurons we show specific transcripts for VEGF and its receptor Flt-1. Finally, we observed that VEGF promotes survival and migration of GN11 cells, a model of migrating GnRH neurons, by activating PI3K and MAPK pathways. These results strongly confirm the existence of a developmental ‘cross-talk’ between the vascular and GnRH-neuronal systems.