Lpd depletion reveals that SRF specifies radial versus tangential migration of pyramidal neurons

During corticogenesis, pyramidal neurons (~80% of cortical neurons) arise from the ventricular zone, pass through a multipolar stage to become bipolar and attach to radial glia[superscript 1, 2], and then migrate to their proper position within the cortex[superscript 1, 3]. As pyramidal neurons migr...

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Main Authors: Pinheiro, Elaine M., Xie, Zhigang, Norovich, Amy L., Vidaki, Marina, Tsai, Li-Huei, Gertler, Frank
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Nature Publishing Group 2012
Online Access:http://hdl.handle.net/1721.1/71220
https://orcid.org/0000-0003-1262-0592
https://orcid.org/0000-0003-3214-4554
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author Pinheiro, Elaine M.
Xie, Zhigang
Norovich, Amy L.
Vidaki, Marina
Tsai, Li-Huei
Gertler, Frank
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Pinheiro, Elaine M.
Xie, Zhigang
Norovich, Amy L.
Vidaki, Marina
Tsai, Li-Huei
Gertler, Frank
author_sort Pinheiro, Elaine M.
collection MIT
description During corticogenesis, pyramidal neurons (~80% of cortical neurons) arise from the ventricular zone, pass through a multipolar stage to become bipolar and attach to radial glia[superscript 1, 2], and then migrate to their proper position within the cortex[superscript 1, 3]. As pyramidal neurons migrate radially, they remain attached to their glial substrate as they pass through the subventricular and intermediate zones, regions rich in tangentially migrating interneurons and axon fibre tracts. We examined the role of lamellipodin (Lpd), a homologue of a key regulator of neuronal migration and polarization in Caenorhabditis elegans, in corticogenesis. Lpd depletion caused bipolar pyramidal neurons to adopt a tangential, rather than radial-glial, migration mode without affecting cell fate. Mechanistically, Lpd depletion reduced the activity of SRF, a transcription factor regulated by changes in the ratio of polymerized to unpolymerized actin. Therefore, Lpd depletion exposes a role for SRF in directing pyramidal neurons to select a radial migration pathway along glia rather than a tangential migration mode.
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spelling mit-1721.1/712202022-01-18T18:22:25Z Lpd depletion reveals that SRF specifies radial versus tangential migration of pyramidal neurons Pinheiro, Elaine M. Xie, Zhigang Norovich, Amy L. Vidaki, Marina Tsai, Li-Huei Gertler, Frank Massachusetts Institute of Technology. Department of Biology Picower Institute for Learning and Memory Koch Institute for Integrative Cancer Research at MIT Tsai, Li-Huei Pinheiro, Elaine M. Xie, Zhigang Norovich, Amy L. Vidaki, Marina Tsai, Li-Huei Gertler, Frank During corticogenesis, pyramidal neurons (~80% of cortical neurons) arise from the ventricular zone, pass through a multipolar stage to become bipolar and attach to radial glia[superscript 1, 2], and then migrate to their proper position within the cortex[superscript 1, 3]. As pyramidal neurons migrate radially, they remain attached to their glial substrate as they pass through the subventricular and intermediate zones, regions rich in tangentially migrating interneurons and axon fibre tracts. We examined the role of lamellipodin (Lpd), a homologue of a key regulator of neuronal migration and polarization in Caenorhabditis elegans, in corticogenesis. Lpd depletion caused bipolar pyramidal neurons to adopt a tangential, rather than radial-glial, migration mode without affecting cell fate. Mechanistically, Lpd depletion reduced the activity of SRF, a transcription factor regulated by changes in the ratio of polymerized to unpolymerized actin. Therefore, Lpd depletion exposes a role for SRF in directing pyramidal neurons to select a radial migration pathway along glia rather than a tangential migration mode. Ruth L. Kirschstein National Research Service Award (grant F32- GM074507) National Institutes of Health (U.S.) (grant # GM068678) 2012-06-27T17:39:26Z 2012-06-27T17:39:26Z 2011-07 2010-10 Article http://purl.org/eprint/type/JournalArticle 1465-7392 1476-4679 http://hdl.handle.net/1721.1/71220 Pinheiro, Elaine M. et al. “Lpd Depletion Reveals That SRF Specifies Radial Versus Tangential Migration of Pyramidal Neurons.” Nature Cell Biology 13.8 (2011): 989–995. Web. 27 June 2012. https://orcid.org/0000-0003-1262-0592 https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1038/ncb2292 Nature Cell Biology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PubMed Central
spellingShingle Pinheiro, Elaine M.
Xie, Zhigang
Norovich, Amy L.
Vidaki, Marina
Tsai, Li-Huei
Gertler, Frank
Lpd depletion reveals that SRF specifies radial versus tangential migration of pyramidal neurons
title Lpd depletion reveals that SRF specifies radial versus tangential migration of pyramidal neurons
title_full Lpd depletion reveals that SRF specifies radial versus tangential migration of pyramidal neurons
title_fullStr Lpd depletion reveals that SRF specifies radial versus tangential migration of pyramidal neurons
title_full_unstemmed Lpd depletion reveals that SRF specifies radial versus tangential migration of pyramidal neurons
title_short Lpd depletion reveals that SRF specifies radial versus tangential migration of pyramidal neurons
title_sort lpd depletion reveals that srf specifies radial versus tangential migration of pyramidal neurons
url http://hdl.handle.net/1721.1/71220
https://orcid.org/0000-0003-1262-0592
https://orcid.org/0000-0003-3214-4554
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