title: Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice.
abstract: Cortical interneurons are generated predominantly in the medial ganglionic eminence (MGE) and migrate through the ventral and dorsal telencephalon before taking their final positions within the developing cortical plate. Previously we demonstrated that interneurons from Robo1 knockout (Robo1(-/-)) mice contain reduced levels of neuropilin 1 (Nrp1) and PlexinA1 receptors, rendering them less responsive to the chemorepulsive actions of semaphorin ligands expressed in the striatum and affecting their course of migration (Hernandez-Miranda et al. [2011] J. Neurosci. 31:6174-6187). Earlier studies have highlighted the importance of Nrp1 and Nrp2 in interneuron migration, and here we assess the role of PlexinA1 in this process. We observed significantly fewer cells expressing the interneuron markers Gad67 and Lhx6 in the cortex of PlexinA1(-/-) mice compared with wild-type littermates at E14.5 and E18.5. Although the level of apoptosis was similar in the mutant and control forebrain, proliferation was significantly reduced in the former. Furthermore, progenitor cells in the MGE of PlexinA1(-/-) mice appeared to be poorly anchored to the ventricular surface and showed reduced adhesive properties, which may account for the observed reduction in proliferation. Together our data uncover a novel role for PlexinA1 in forebrain development.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom.
authors.forename: William D
authors.initials: WD
authors.lastname: Andrews
authors.affiliation: Division of Visual Science and Molecular Genetics, Institute of Ophthalmology, University College London, London, WC1E 6BT, United Kingdom.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Davidson
authors.affiliation: Department of Morphological Neural Science, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, 860 0862, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tamamaki
authors.affiliation: Division of Visual Science and Molecular Genetics, Institute of Ophthalmology, University College London, London, WC1E 6BT, United Kingdom.
authors.forename: Christiana
authors.initials: C
authors.lastname: Ruhrberg
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom.
authors.forename: John G
authors.initials: JG
authors.lastname: Parnavelas
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000166:cytology / Q000502:physiology; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C498504:LHX6 protein, mouse; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; C492114:Plxna1 protein, mouse; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: Plexin; forebrain; interneurons; neuronal migration; proliferation