Poster Presentation The International Congress of Neuroendocrinology 2014

Neuropilin-1 expression in GnRH neurons is required for the normal onset of puberty and GnRH cells distribution (#365)

Charlotte Vanacker 1 , Filippo Casoni 1 , Naresh Kumar Hanchate 1 , Paolo Giacobini 1 , Vincent Prevot 1
  1. University of Lille2, Lille, CEDEX, France

Semaphorin3A (Sema3A) and its receptor, neuropilin 1 (Nrp1), are involved in the guidance of GnRH neuron migration during embryogenesis. Disruption of Sema3A gene expression or of neuropilin 1 signaling indeed causes marked GnRH migratory defects in mice. However, the specific role of Nrp1 expression in GnRH neurons remains to be elucidated. Here, we analyse the phenotype of mice in which Nrp1 expression was selectively knocked out in GnRH neurons. Animals harbouring the conditional Nrp1 allele were crossed with a mouse line expressing the Cre recombinase under the control of the endogenous GnRH gene promoter. The efficacy of our genetic strategy was verified by analysing Nrp1 expression in GnRH neurons of wild-type (Nrp1lox/lox) and mutant (GnRH-Cre; Nrp1lox/lox) littermates by immunofluorescence. Unexpectedly, mutant mice that did not show any alteration of adult reproductive function exhibited precocious puberty. While wild-type mice reach puberty (first ovulation) at postnatal day 50 (P50), mutant mice first ovulate at P45. Our preliminary neuroanatomical data suggest that while there is no overt difference in the total number of GnRH neurons in the brain, their distribution appear to differ between mutant mice and wild-type littermates. This phenomenon is probably due to a differential migration of the cells during embryogenesis, since we have already noted differences in GnRH neuronal migration from nose to brain at embryonic age 14,5. Even though further analyses are required to determine the causes of this precocious puberty, the present study is the first report indicating that Nrp1 expression in GnRH neurons plays a role in the correct development/physiology of the GnRH system.