2007/01/10 by Paolo Giacobini, Andrea Messina, Susan Wray +4 · 3 citations
Neuroscience · Medicine · #Axon Guidance and Neuronal Signaling #Neurogenesis and neuroplasticity mechanisms #Growth Hormone and Insulin-like Growth Factors #Hepatocyte growth factor #Internal medicine #Endocrinology #Biology #Gonadotropin-releasing hormone #Cell migration #Cell biology #Plasminogen activator #Hormone #Cell culture #Receptor #Luteinizing hormone #Medicine
paper · pdf · doi:10.1523/jneurosci.4979-06.2007
openalex publication_date 2007/01/10 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Reproduction in mammals is under the control of the hypothalamic neuropeptide gonadotropin hormone-releasing hormone-1 (GnRH-1). GnRH-1-secreting neurons originate during embryonic development in the nasal placode and migrate into the forebrain along olfactory nerves. Gradients of secreted molecules may play a role in this migratory process. In this context, hepatocyte growth factor (HGF) is a potential candidate, because it promotes cell motility in developing brain and has been shown previously to act as a motogen on immortalized GnRH-1 neurons (GN11). In this study, the role of HGF and its receptor Met during development of the GnRH-1 system was examined. GnRH-1 cells express Met during their migration and downregulate its expression once they complete this process. Tissue-type plasminogen activator (tPA), a known HGF activator, is also detected in migratory GnRH-1 neurons. Consistent with in vivo expression, HGF is present in nasal explants, and GnRH-1 neurons express Met. HGF-neutralizing antibody was applied to explants to examine the role of the endogenous growth factor. Migration of GnRH-1 cells and olfactory axon outgrowth were significantly reduced, in line with disruption of a guidance gradient. Exogenous application of HGF to explants increased the distance that GnRH-1 cells migrated, suggesting that HGF also acts as a motogen to GnRH-1 neurons. Functional experiments, performed on organotypic slice cultures, show that creation of an opposing HGF gradient inhibits GnRH-1 neuronal migration. Finally, tPA(-/-):uPA(-/-) (urokinase-type plasminogen activator(-/-)) knock-out mice exhibit strong reduction of the GnRH-1 cell population. Together, these data indicate that HGF signaling via Met receptor influences the development of GnRH-1.