title: RGMB and neogenin control cell differentiation in the developing olfactory epithelium.
abstract: Cellular interactions are key for the differentiation of distinct cell types within developing epithelia, yet the molecular mechanisms engaged in these interactions remain poorly understood. In the developing olfactory epithelium (OE), neural stem/progenitor cells give rise to odorant-detecting olfactory receptor neurons (ORNs) and glial-like sustentacular (SUS) cells. Here, we show in mice that the transmembrane receptor neogenin (NEO1) and its membrane-bound ligand RGMB control the balance of neurons and glial cells produced in the OE. In this layered epithelium, neogenin is expressed in progenitor cells, while RGMB is restricted to adjacent newly born ORNs. Ablation of Rgmb via gene-targeting increases the number of dividing progenitor cells in the OE and leads to supernumerary SUS cells. Neogenin loss-of-function phenocopies these effects observed in Rgmb(-/-) mice, supporting the proposal that RGMB-neogenin signaling regulates progenitor cell numbers and SUS cell production. Interestingly, Neo1(-/-) mice also exhibit increased apoptosis of ORNs, implicating additional ligands in the neogenin-dependent survival of ORNs. Thus, our results indicate that RGMB-neogenin-mediated cell-cell interactions between newly born neurons and progenitor cells control the ratio of glia and neurons produced in the OE.
authors.affiliation: Montreal Neurological Institute, 3801 University, Montréal, Québec, Canada H3A 2B4 Department of Neurology and Neurosurgery, McGill University, 3801 University, Montréal, Québec, Canada H3A 2B4.
authors.forename: Joseph Wai Keung
authors.initials: JW
authors.lastname: Kam
authors.affiliation: Montreal Neurological Institute, 3801 University, Montréal, Québec, Canada H3A 2B4 Department of Neurology and Neurosurgery, McGill University, 3801 University, Montréal, Québec, Canada H3A 2B4.
authors.forename: Emilie
authors.initials: E
authors.lastname: Dumontier
authors.affiliation: Montreal Neurological Institute, 3801 University, Montréal, Québec, Canada H3A 2B4 Department of Neurology and Neurosurgery, McGill University, 3801 University, Montréal, Québec, Canada H3A 2B4.
authors.forename: Christopher
authors.initials: C
authors.lastname: Baim
authors.affiliation: Montreal Neurological Institute, 3801 University, Montréal, Québec, Canada H3A 2B4 Department of Neurology and Neurosurgery, McGill University, 3801 University, Montréal, Québec, Canada H3A 2B4.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Brignall
authors.affiliation: Montreal Neurological Institute, 3801 University, Montréal, Québec, Canada H3A 2B4 Center for Neuroscience and Cell Biology and Department of Life Sciences, University of Coimbra, Rua Larga, Coimbra 3004-517, Portugal.
authors.forename: David
authors.initials: D
authors.lastname: Mendes da Silva
authors.affiliation: Centre de Recherches du Centre Hospitalier de l'Université de Montréal, 900 rue Saint-Denis, Montréal, Canada H2X 0A9.
authors.forename: Mitra
authors.initials: M
authors.lastname: Cowan
authors.affiliation: Montreal Neurological Institute, 3801 University, Montréal, Québec, Canada H3A 2B4 Department of Neurology and Neurosurgery, McGill University, 3801 University, Montréal, Québec, Canada H3A 2B4 Department of Anatomy and Cell Biology, McGill University, 3640 University, Montréal, Québec, Canada H3A 0C7.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Kennedy
authors.affiliation: Montreal Neurological Institute, 3801 University, Montréal, Québec, Canada H3A 2B4 Department of Neurology and Neurosurgery, McGill University, 3801 University, Montréal, Québec, Canada H3A 2B4 Department of Anatomy and Cell Biology, McGill University, 3640 University, Montréal, Québec, Canada H3A 0C7 jf.cloutier@mcgill.ca.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Cloutier
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal; D049109:Cell Proliferation / Q000235:genetics; D058851:GPI-Linked Proteins; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000235:genetics* / Q000502:physiology; D009457:Neuroglia / Q000166:cytology; D009831:Olfactory Mucosa / Q000166:cytology / Q000196:embryology*; D018034:Olfactory Receptor Neurons / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C483497:Rgmb protein, mouse; C091279:neogenin
keywords: Cellular differentiation; Gliogenesis; Mouse; Neogenin; Neurogenesis; Olfactory epithelium; RGM