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], [superscript 2], and then migrate to their proper position within the cortex[superscript 1], [superscript 3...

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Main Authors: Pinheiro, Elaine M., Xie, Zhigang, Norovich, Amy L., Vidaki, Marina, Tsai, Li-Huei, Gertler, Frank
Other Authors: Picower Institute for Learning and Memory
Format: Article
Language:en_US
Published: Nature Publishing Group 2012
Online Access:http://hdl.handle.net/1721.1/73532
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 Picower Institute for Learning and Memory
author_facet Picower Institute for Learning and Memory
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], [superscript 2], and then migrate to their proper position within the cortex[superscript 1], [superscript 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-1721.1/735322022-01-18T17:48:55Z 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 Picower Institute for Learning and Memory Koch Institute for Integrative Cancer Research at MIT Pinheiro, Elaine M. 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], [superscript 2], and then migrate to their proper position within the cortex[superscript 1], [superscript 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) Howard Hughes Medical Institute (Investigator) David H. Koch Institute for Integrative Cancer Research at MIT (Development Award) 2012-10-02T12:27:27Z 2012-10-02T12:27:27Z 2011-07 2010-10 Article http://purl.org/eprint/type/JournalArticle 1465-7392 1476-4679 http://hdl.handle.net/1721.1/73532 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. 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 PMC
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/1721.1/73532
https://orcid.org/0000-0003-1262-0592
https://orcid.org/0000-0003-3214-4554
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