Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice.
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.
['Andrews|William D|WD|', 'Davidson|Kathryn|K|', 'Tamamaki|Nobuaki|N|', 'Ruhrberg|Christiana|C|', 'Parnavelas|John G|JG|']
D000818:Animals D017209:Apoptosis D002448:Cell Adhesion D002465:Cell Movement D049109:Cell Proliferation D002478:Cells, Cultured D002540:Cerebral Cortex D005968:Glutamate Decarboxylase D049452:Green Fluorescent Proteins D007150:Immunohistochemistry D017403:In Situ Hybridization D007395:Interneurons D060850:LIM-Homeodomain Proteins D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009419:Nerve Tissue Proteins D058953:Neural Stem Cells D055495:Neurogenesis D011956:Receptors, Cell Surface D014157:Transcription Factors
interneurons forebrain proliferation Plexin neuronal migration