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Published online November 3, 2008
doi:10.1083/jcb.200806160
The Journal of Cell Biology, Vol. 183, No. 3, 555-566
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Giacobini et al.
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Article

Semaphorin 4D regulates gonadotropin hormone–releasing hormone-1 neuronal migration through PlexinB1–Met complex



Paolo Giacobini1, Andrea Messina1, Francesca Morello1, Nicoletta Ferraris1, Simona Corso2, Junia Penachioni2, Silvia Giordano2, Luca Tamagnone2, and Aldo Fasolo1,3

1 Department of Human and Animal Biology, University of Turin, Turin 10123 Italy
2 Institute for Cancer Research and Treatment, University of Turin Medical School, Candiolo, Turin 10060 Italy
3 National Institute of Neuroscience, Turin 10125, Italy

Correspondence to Paolo Giacobini: paolo.giacobini{at}unito.it

In mammals, reproduction is dependent on specific neurons secreting the neuropeptide gonadotropin hormone–releasing hormone-1 (GnRH-1). These cells originate during embryonic development in the olfactory placode and migrate into the forebrain, where they become integral members of the hypothalamic–pituitary–gonadal axis. This migratory process is regulated by a wide range of guidance cues, which allow GnRH-1 cells to travel over long distances to reach their appropriate destinations. The Semaphorin4D (Sema4D) receptor, PlexinB1, is highly expressed in the developing olfactory placode, but its function in this context is still unknown. Here, we demonstrate that PlexinB1-deficient mice exhibit a migratory defect of GnRH-1 neurons, resulting in reduction of this cell population in the adult brain. Moreover, Sema4D promotes directional migration in GnRH-1 cells by coupling PlexinB1 with activation of the Met tyrosine kinase (hepatocyte growth factor receptor). This work identifies a function for PlexinB1 during brain development and provides evidence that Sema4D controls migration of GnRH-1 neurons.

P. Giacobini and A. Messina contributed equally to this paper.

Abbreviations used in this paper: ANOVA, analysis of variance; cntr, control; div, days in vitro; E, embryonic day; GnRH-1, gonadotropin hormone–releasing hormone-1; HGF, hepatocyte growth factor; IHH, idiopathic hypogonadotropic hypogonadisms; KO, knockout; NCAM, neural cell adhesion molecule; OE, olfactory epithelium; P, postnatal day; PHA, PHA-665752; Sema4D, Semaphorin4D; shRNA, short hairpin RNA; VNO, vomeronasal organ; WT, wild type.

© 2008 Giacobini et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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