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

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.

[1]  R. Pasterkamp,et al.  Semaphorin signaling: progress made and promises ahead. , 2008, Trends in biochemical sciences.

[2]  S. Offermanns,et al.  ErbB-2 and Met Reciprocally Regulate Cellular Signaling via Plexin-B1* , 2008, Journal of Biological Chemistry.

[3]  P. Comoglio,et al.  Silencing the MET oncogene leads to regression of experimental tumors and metastases , 2008, Oncogene.

[4]  P. Bouloux,et al.  Diversity in Fibroblast Growth Factor Receptor 1 Regulation: Learning from the Investigation of Kallmann Syndrome , 2007, Journal of neuroendocrinology.

[5]  A. Kolodkin,et al.  Semaphorin regulation of cellular morphology. , 2007, Annual review of cell and developmental biology.

[6]  S. Tobet,et al.  Gonadotropin-releasing hormone neuronal migration. , 2007, Seminars in reproductive medicine.

[7]  A. Kolodkin,et al.  Expression patterns of semaphorin7A and plexinC1 during rat neural development suggest roles in axon guidance and neuronal migration , 2007, BMC Developmental Biology.

[8]  S. Offermanns,et al.  Plexin-B2, But Not Plexin-B1, Critically Modulates Neuronal Migration and Patterning of the Developing Nervous System In Vivo , 2007, The Journal of Neuroscience.

[9]  F. Rossi,et al.  Plexin-B1 plays a redundant role during mouse development and in tumour angiogenesis , 2007, BMC Developmental Biology.

[10]  C. Sotelo,et al.  Plexin-B2 Controls the Development of Cerebellar Granule Cells , 2007, The Journal of Neuroscience.

[11]  S. Tischkau,et al.  Neuropilins and Their Ligands Are Important in the Migration of Gonadotropin-Releasing Hormone Neurons , 2007, The Journal of Neuroscience.

[12]  P. Carmeliet,et al.  Hepatocyte Growth Factor Acts as a Motogen and Guidance Signal for Gonadotropin Hormone-Releasing Hormone-1 Neuronal Migration , 2007, The Journal of Neuroscience.

[13]  G. Menon,et al.  Particle-Mediated Gene Delivery and Human Skin: Ultrastructural Observations on Stratum Corneum Barrier Structures , 2006, Skin Pharmacology and Physiology.

[14]  S. Tobet,et al.  Stromal Cell-Derived Factor-1 (Chemokine C-X-C Motif Ligand 12) and Chemokine C-X-C Motif Receptor 4 Are Required for Migration of Gonadotropin-Releasing Hormone Neurons to the Forebrain , 2006, The Journal of Neuroscience.

[15]  H. Katoh,et al.  Semaphorin 4D/Plexin-B1–mediated R-Ras GAP activity inhibits cell migration by regulating β1 integrin activity , 2006, The Journal of cell biology.

[16]  A. Goffinet,et al.  Reelin provides an inhibitory signal in the migration of gonadotropin-releasing hormone neurons , 2005, Development.

[17]  P. Comoglio,et al.  Articles on similar topics can be found in the following Blood collections , 2004 .

[18]  M. Todman,et al.  Disruption of Ephrin Signaling Associates with Disordered Axophilic Migration of the Gonadotropin-Releasing Hormone Neurons , 2005, The Journal of Neuroscience.

[19]  H. Sariola,et al.  The expression of plexins during mouse embryogenesis. , 2005, Gene expression patterns : GEP.

[20]  P. Comoglio,et al.  Interplay between scatter factor receptors and B plexins controls invasive growth , 2004, Oncogene.

[21]  P. Bouloux,et al.  Ontogeny of GnRH and olfactory neuronal systems in man: novel insights from the investigation of inherited forms of Kallmann’s syndrome , 2004, Frontiers in Neuroendocrinology.

[22]  S. Offermanns,et al.  Plexin-B1/RhoGEF–mediated RhoA activation involves the receptor tyrosine kinase ErbB-2 , 2004, The Journal of cell biology.

[23]  S. Offermanns,et al.  Plexin‐B family members demonstrate non‐redundant expression patterns in the developing mouse nervous system: an anatomical basis for morphogenetic effects of Sema4D during development , 2004, The European journal of neuroscience.

[24]  P. Comoglio,et al.  Plexin signaling hampers integrin‐based adhesion, leading to Rho‐kinase independent cell rounding, and inhibiting lamellipodia extension and cell motility , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[25]  S. Ackerman,et al.  Netrin 1‐mediated chemoattraction regulates the migratory pathway of LHRH neurons , 2004, The European journal of neuroscience.

[26]  J. Christensen,et al.  A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. , 2003, Cancer research.

[27]  Jacques J. Peschon,et al.  Semaphorin 7A promotes axon outgrowth through integrins and MAPKs , 2003, Nature.

[28]  P. Comoglio,et al.  Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. , 2003, Cancer cell.

[29]  P. Comoglio,et al.  Functional Regulation of Semaphorin Receptors by Proprotein Convertases* , 2003, The Journal of Biological Chemistry.

[30]  Giorgio F. Gilestro,et al.  The Semaphorin 4D receptor controls invasive growth by coupling with Met , 2002, Nature Cell Biology.

[31]  A. Fasolo,et al.  Hepatocyte growth factor/scatter factor facilitates migration of GN-11 immortalized LHRH neurons. , 2002, Endocrinology.

[32]  S. Offermanns,et al.  Plexin-B1 Directly Interacts with PDZ-RhoGEF/LARG to Regulate RhoA and Growth Cone Morphology , 2002, Neuron.

[33]  S. Wray Development of gonadotropin-releasing hormone-1 neurons , 2002, Frontiers in Neuroendocrinology.

[34]  A. Elhabazi,et al.  Biological Activity of Soluble CD100. I. The Extracellular Region of CD100 Is Released from the Surface of T Lymphocytes by Regulated Proteolysis1 , 2001, The Journal of Immunology.

[35]  S. Tobet,et al.  Deleted in Colorectal Cancer (DCC) Regulates the Migration of Luteinizing Hormone-Releasing Hormone Neurons to the Basal Forebrain , 2001, The Journal of Neuroscience.

[36]  M. Ikawa,et al.  The class IV semaphorin CD100 plays nonredundant roles in the immune system: defective B and T cell activation in CD100-deficient mice. , 2000, Immunity.

[37]  L. Naldini,et al.  Lentiviral vectors: excellent tools for experimental gene transfer and promising candidates for gene therapy , 2000, The journal of gene medicine.

[38]  S. Wray,et al.  Novel gene expressed in nasal region influences outgrowth of olfactory axons and migration of luteinizing hormone-releasing hormone (LHRH) neurons. , 2000, Genes & development.

[39]  S. Wray,et al.  Transcription factor activator protein-2 is required for continued luteinizing hormone-releasing hormone expression in the forebrain of developing mice. , 2000, Endocrinology.

[40]  G. Ronnett,et al.  Expression of neuron-specific beta-III tubulin during olfactory neurogenesis in the embryonic and adult rat , 1998, Neuroscience.

[41]  D. Thewke,et al.  Expression of Hepatocyte Growth Factor/Scatter Factor, Its Receptor, c-met, and Tissue-Type Plasminogen Activator during Development of the Murine Olfactory System , 1996, The Journal of Neuroscience.

[42]  F. Valverde,et al.  Early olfactory fiber projections and cell migration into the rat telencephalon , 1996, International Journal of Developmental Neuroscience.

[43]  K. Yoshida,et al.  The migration of luteinizing hormone-releasing hormone neurons in the developing rat is associated with a transient, caudal projection of the vomeronasal nerve , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[44]  S. Wray,et al.  LHRH cells migrate on peripherin fibers in embryonic olfactory explant cultures: an in vitro model for neurophilic neuronal migration. , 1994, Developmental biology.

[45]  F. Wondisford,et al.  Migratory arrest of gonadotropin-releasing hormone neurons in transgenic mice. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[46]  H. Gainer,et al.  Evidence that cells expressing luteinizing hormone-releasing hormone mRNA in the mouse are derived from progenitor cells in the olfactory placode. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[47]  A. Calof,et al.  Analysis of neurogenesis in a mammalian neuroepithelium: Proliferation and differentiation of an olfactory neuron precursor in vitro , 1989, Neuron.

[48]  D. Pfaff,et al.  Origin of luteinizing hormone-releasing hormone neurons , 1989, Nature.

[49]  B. Gähwiler,et al.  Slice cultures of LHRH neurons in the presence and absence of brainstem and pituitary , 1988, Peptides.

[50]  A. Herbison,et al.  Gonadotropin-releasing hormone (GnRH) neuron requirements for puberty, ovulation and fertility , 2018 .

[51]  Yu-Qiang Ding,et al.  Semaphorin-3A guides radial migration of cortical neurons during development , 2008, Nature Neuroscience.

[52]  L. Tamagnone,et al.  Semaphorin signals in cell adhesion and cell migration: functional role and molecular mechanisms. , 2007, Advances in experimental medicine and biology.

[53]  P. Comoglio,et al.  Sema 4 D induces angiogenesis through Met recruitment by Plexin B 1 , 2005 .