Factors involved in the migration of neuroendocrine hypothalamic neurons

Roberto Maggi, A. Cariboni, R. Zaninetti, A. Samara, F. Stossi, F. Pimpinelli, P. Giacobini, G. G. Consalez, E. Rugarli, F. Piva

Research output: Contribution to journalArticle

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Abstract

Neuroendocrine control of physiological functions needs a complex developmental organisation of the hypothalamic parvicellular neurons, which synthesise and release hypophysiotropic hormones. Among the hypothalamic neuroendocrine cells, Gonadotropin-releasing hormone (GnRH) neurons represent a unique class; they are generated in the olfactory placode and, during embryonic life, migrate to the septo/hypothalamic region along terminal and vomeronasal nerves. At this level GnRH neurons undergo terminal differentiation and start to release GnRH to modulate the secretion of pituitary gonadotropins. All these steps are under the strict control of several developmental cues and their defect might represent a cause of clinical disorders. A number of factors have been proposed to be involved in the migration of GnRH neurons, but their role is still unclear. By using gene knockout techniques it has been found that mice carrying a targeted deletion of Ebf2 gene, a component of Olf/Ebf bHLH transcription factors, show a defective migration of GnRH neurons, providing the first evidence of a mouse model of such defect. Since the investigation of GnRH neurons is hindered by their peculiar anatomical distribution, other studies has been forwarded by the availability of immortalized GnRH-expressing neurons (GN11 cells) that retain a strong chemomigratory response "in vitro". Among the factors analysed, we found that hepatocyte growth factor/scatter factor (HGF/SF) and vascular endothelial growth factor (VEGF) induce specific chemotaxis of GN11 neurons, suggesting that migratory signals can arise from nasal mesenchyme and from the concomitant vasculogenesis. Finally, anosmin-1 (the product of the gene responsible of the X-linked form of Kallmann's disease) was found to induce a significant chemotactic response of GN11 cells, confirming a permissive/instructive role of KAL1 gene product in the migratory behaviour of GnRH neurons. In conclusion, the migration of the GnRH neurons appears to be a complex process, which involves the interplay of multiple molecular cues. These studies may provide new insights on the etiopathogenesis of the large proportion of reproductive dysfunctions that affect humans and could provide novel insights on common biochemical events controlling neuronal development and migration.

Original languageEnglish
Pages (from-to)171-178
Number of pages8
JournalArchives Italiennes de Biologie
Volume143
Issue number3-4
Publication statusPublished - Sep 2005

Fingerprint

Gonadotropin-Releasing Hormone
Neurons
Hepatocyte Growth Factor
Cues
Vomeronasal Organ
Pituitary Hormone-Releasing Hormones
Gene Components
Basic Helix-Loop-Helix Transcription Factors
Pituitary Gonadotropins
Neuroendocrine Cells
X-Linked Genes
Gene Knockout Techniques
Mesoderm
Chemotaxis
Nose
Vascular Endothelial Growth Factor A
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Maggi, R., Cariboni, A., Zaninetti, R., Samara, A., Stossi, F., Pimpinelli, F., ... Piva, F. (2005). Factors involved in the migration of neuroendocrine hypothalamic neurons. Archives Italiennes de Biologie, 143(3-4), 171-178.

Factors involved in the migration of neuroendocrine hypothalamic neurons. / Maggi, Roberto; Cariboni, A.; Zaninetti, R.; Samara, A.; Stossi, F.; Pimpinelli, F.; Giacobini, P.; Consalez, G. G.; Rugarli, E.; Piva, F.

In: Archives Italiennes de Biologie, Vol. 143, No. 3-4, 09.2005, p. 171-178.

Research output: Contribution to journalArticle

Maggi, R, Cariboni, A, Zaninetti, R, Samara, A, Stossi, F, Pimpinelli, F, Giacobini, P, Consalez, GG, Rugarli, E & Piva, F 2005, 'Factors involved in the migration of neuroendocrine hypothalamic neurons', Archives Italiennes de Biologie, vol. 143, no. 3-4, pp. 171-178.
Maggi R, Cariboni A, Zaninetti R, Samara A, Stossi F, Pimpinelli F et al. Factors involved in the migration of neuroendocrine hypothalamic neurons. Archives Italiennes de Biologie. 2005 Sep;143(3-4):171-178.
Maggi, Roberto ; Cariboni, A. ; Zaninetti, R. ; Samara, A. ; Stossi, F. ; Pimpinelli, F. ; Giacobini, P. ; Consalez, G. G. ; Rugarli, E. ; Piva, F. / Factors involved in the migration of neuroendocrine hypothalamic neurons. In: Archives Italiennes de Biologie. 2005 ; Vol. 143, No. 3-4. pp. 171-178.
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