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[P57]: A simple method for directing the differentiation of embryonic stem (ES) cells into functional motoneurones
Author(s) -
Soundararajan P.,
Lindsey B.,
Rafuse V.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.120
Subject(s) - citation , library science , simple (philosophy) , embryonic stem cell , computer science , sociology , biology , philosophy , epistemology , genetics , gene
Gap junctions, aqueous pores that couple cells and allow the exchange of electrical current as well as small molecules, are expressed in cortical stem and progenitor cells as well as in migrating neurons. By allowing communication among progenitors or between progenitors and neuroblasts, gap junctions are thought to play a role in regulating cortical development. The specific roles of gap junctions remain poorly understood partly because interpretation of data from previous studies is confounded by compensation and lethality in knockout mice and by the lack of selectivity and specificity of pharmological agents that interact with gap junctions. In order to determine the role of gap junctions in corticogenesis, we developed short hairpin RNAs (shRNAs) to acutely down-regulate the expression of the gap junction subunits connexin-26 and connexin-43, which are known to be expressed in embryonic neural stem and progenitor cells. We introduced shRNA plasmids into the intact embryonic rat cerebral cortex using in utero, intraventricular injection and electroporation. These acute loss-of-function experiments demonstate novel roles for gap junctions in regulating cell cycle, mediating the migration of neurons to the cortical plate, and determinging cell fate. These loss-of-function pheotypes demonstrate that gap junctions play a critical role in multiple aspects of cortical development.