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Downregulation of L1 perturbs neuronal migration and alters the expression of transcription factors in murine neocortex
Author(s) -
Kishimoto Tomokazu,
Itoh Kyoko,
Umekage Masafumi,
Tonosaki Madoka,
Yaoi Takeshi,
Fukui Kenji,
Lemmon Vance P.,
Fushiki Shinji
Publication year - 2013
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23141
Subject(s) - small hairpin rna , transfection , biology , neocortex , electroporation , microbiology and biotechnology , embryonic stem cell , neuroscience , cell culture , gene knockdown , gene , genetics , biochemistry
L1 is a cell adhesion molecule associated with a spectrum of human neurological diseases, the most well‐known being X‐linked hydrocephalus. L1 knockout (L1‐KO) mice have revealed a variety of functions of L1 that were crucial in brain development in different brain regions. However; the function of L1 in neuronal migration during cortical histogenesis remains to be clarified. We therefore investigated the corticogenesis of mouse embryos in which L1 molecules were knocked down in selected neurons, by employing in utero electroporation with shRNAs targeting L1 (L1 shRNA). Although more than 50% of the cells transfected with no small hairpin RNA (shRNA; monster green fluorescent protein: MGFP only) vector at embryonic day 13 (E13) reached the cortical plate at E16, significantly fewer (27%) cells transfected with L1 shRNA migrated to the same extent. At E17, 22% of cells transfected with the MGFP‐only vector were found in the intermediate zone, and significantly more (34%) cells transfected with L1 shRNA remained in the same zone. Furthermore, the directions of the leading process of neurons transfected with L1 shRNA became more dispersed compared with cells with the MGFP‐only vector. In addition, two transcription factors expressed in the neurons, Satb2 and Tbr1, were shown to be reduced or aberrantly expressed in neurons transfected with L1 shRNA. These observations suggest that L1 plays an important role in regulating the locomotion and orientation of migrating neurons and the expression of transcription factors during neocortical development that might partially be responsible for the abnormal tract formation seen in L1‐KO mice. © 2012 Wiley Periodicals, Inc.