title: Neuregulin1 alpha activates migration of neuronal progenitors expressing ErbB4.
abstract: Deficits in neuronal migration during development in the central nervous system may contribute to psychiatric diseases. The ligand neuregulin1 (NRG1) and its receptor ErbB4 are genes conferring susceptibility to schizophrenia, playing a key role in the control of neuronal migration both during development and adulthood. Several NRG1 and ErbB4 isoforms were identified, which deeply differ in their characteristics. Here we focused on the four ErbB4 isoforms and the two NRG1 isoforms differing in their EGF-like domain, namely α and β. We hypothesized that these isoforms, which are differently regulated in schizophrenic patients, could play different roles in neuronal migration. Our hypothesis was strengthened by the observation that both NRG1α and NRG1β and the four ErbB4 isoforms are expressed in the medial and lateral ganglionic eminences and in the cortex during development in rat. We analysed in vitro the signal transduction pathways activated by the different ErbB4 isoforms following the treatment with soluble recombinant NRG1α or NRG1β and the ability to stimulate migration. Our data show that two ErbB4 isoforms, namely JMa-cyt2 and JMb-cyt1, following NRG1α and NRG1β treatment, strongly activate AKT phosphorylation, conferring high migratory activity to neuronal progenitors, thus demonstrating that both NRG1α and NRG1β can play a role in neuronal migration.
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy; Neuroscience Institute of the "Cavalieri Ottolenghi" Foundation (NICO), University of Torino, Italy.
authors.forename: Benedetta Elena
authors.initials: BE
authors.lastname: Fornasari
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy; Department of Molecular Biology, University of Alexandria, Alexandria, Egypt.
authors.forename: Marwa
authors.initials: M
authors.lastname: El Soury
authors.affiliation: Neuroscience Institute of the "Cavalieri Ottolenghi" Foundation (NICO), University of Torino, Italy; Department of Life Sciences and Systems Biology, University of Torino, Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: De Marchis
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perroteau
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy; Neuroscience Institute of the "Cavalieri Ottolenghi" Foundation (NICO), University of Torino, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Geuna
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy. Electronic address: giovanna.gambarotta@unito.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Gambarotta
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism* / Q000502:physiology; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D066247:Receptor, ErbB-4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D020033:Protein Isoforms; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4; D051057:Proto-Oncogene Proteins c-akt
keywords: Alternative splicing; ErbB4; Neuronal migration; Signal transduction; neuregulin1