Abstract

The central nervous system is fundamentally dependent on guided cell migration, both during development and in adulthood. We report an absolute requirement of the transcription factor serum response factor (SRF) for neuronal migration in the mouse forebrain. Conditional, late-prenatal deletion of Srf causes neurons to accumulate ectopically at the subventricular zone (SVZ), a prime neurogenic region in the brain. SRF-deficient cells of the SVZ exhibit impaired tangential chain migration along the rostral migratory stream into the olfactory bulb. SVZ explants display retarded chain migration in vitro. Regarding target genes, SRF deficiency impairs expression of the β-actin and gelsolin genes, accompanied by reduced cytoskeletal actin fiber density. At the posttranslational level, cofilin, a key regulator of actin dynamics, displays dramatically elevated inhibitory phosphorylation at Ser-3. Our studies indicate that SRF-controlled gene expression directs both the structure and dynamics of the actin microfilament, thereby determining cell-autonomous neuronal migration.

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Acknowledgments

We greatly appreciate excellent technical support by S. Herberich and C. Krüger and useful comments on the manuscript by B. Knöll. We thank W. Witke (European Molecular Biology Laboratory, Monterotondo) for anti-gelsolin antisera and acknowledge insightful discussions with F. Haiss. A.N. was financed by the Deutsche Forschungsgemeinschaft (120/12-1 and SFB446/B7) and the Fonds der Chemischen Industrie. M.F. and O.K. were supported by the Deutsche Forschungsgemeinschaft (SFB505 and TR-3). U.P. received a Ph.D. scholarship from the Boehringer Ingelheim Fonds.

Supporting Information

01191Fig6.jpg

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Information & Authors

Information

Published in

The cover image for PNAS Vol.102; No.17
Proceedings of the National Academy of Sciences
Vol. 102 | No. 17
April 26, 2005
PubMed: 15837932

Classifications

Submission history

Revision received: February 11, 2005
Published online: April 18, 2005
Published in issue: April 26, 2005

Keywords

  1. actin cytoskeleton
  2. cofilin
  3. transcription

Acknowledgments

We greatly appreciate excellent technical support by S. Herberich and C. Krüger and useful comments on the manuscript by B. Knöll. We thank W. Witke (European Molecular Biology Laboratory, Monterotondo) for anti-gelsolin antisera and acknowledge insightful discussions with F. Haiss. A.N. was financed by the Deutsche Forschungsgemeinschaft (120/12-1 and SFB446/B7) and the Fonds der Chemischen Industrie. M.F. and O.K. were supported by the Deutsche Forschungsgemeinschaft (SFB505 and TR-3). U.P. received a Ph.D. scholarship from the Boehringer Ingelheim Fonds.

Authors

Affiliations

Siegfried Alberti
Department of Molecular Biology, Institute for Cell Biology, Tübingen University, 72076 Tübingen, Germany; Institute of Anatomy and Cell Biology, University of Freiburg, 79001 Freiburg, Germany; Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany; and Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany
Sven M. Krause
Department of Molecular Biology, Institute for Cell Biology, Tübingen University, 72076 Tübingen, Germany; Institute of Anatomy and Cell Biology, University of Freiburg, 79001 Freiburg, Germany; Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany; and Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany
Oliver Kretz
Department of Molecular Biology, Institute for Cell Biology, Tübingen University, 72076 Tübingen, Germany; Institute of Anatomy and Cell Biology, University of Freiburg, 79001 Freiburg, Germany; Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany; and Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany
Ulrike Philippar
Department of Molecular Biology, Institute for Cell Biology, Tübingen University, 72076 Tübingen, Germany; Institute of Anatomy and Cell Biology, University of Freiburg, 79001 Freiburg, Germany; Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany; and Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany
Thomas Lemberger
Department of Molecular Biology, Institute for Cell Biology, Tübingen University, 72076 Tübingen, Germany; Institute of Anatomy and Cell Biology, University of Freiburg, 79001 Freiburg, Germany; Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany; and Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany
Emilio Casanova
Department of Molecular Biology, Institute for Cell Biology, Tübingen University, 72076 Tübingen, Germany; Institute of Anatomy and Cell Biology, University of Freiburg, 79001 Freiburg, Germany; Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany; and Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany
Franziska F. Wiebel
Department of Molecular Biology, Institute for Cell Biology, Tübingen University, 72076 Tübingen, Germany; Institute of Anatomy and Cell Biology, University of Freiburg, 79001 Freiburg, Germany; Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany; and Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany
Heinz Schwarz
Department of Molecular Biology, Institute for Cell Biology, Tübingen University, 72076 Tübingen, Germany; Institute of Anatomy and Cell Biology, University of Freiburg, 79001 Freiburg, Germany; Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany; and Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany
Michael Frotscher
Department of Molecular Biology, Institute for Cell Biology, Tübingen University, 72076 Tübingen, Germany; Institute of Anatomy and Cell Biology, University of Freiburg, 79001 Freiburg, Germany; Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany; and Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany
Günther Schütz
Department of Molecular Biology, Institute for Cell Biology, Tübingen University, 72076 Tübingen, Germany; Institute of Anatomy and Cell Biology, University of Freiburg, 79001 Freiburg, Germany; Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany; and Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany
Alfred Nordheim**
Department of Molecular Biology, Institute for Cell Biology, Tübingen University, 72076 Tübingen, Germany; Institute of Anatomy and Cell Biology, University of Freiburg, 79001 Freiburg, Germany; Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany; and Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany

Notes

**
To whom correspondence should be addressed at: Tübingen University, Interfakultäres Institut für Zellbiologie, Abteilung Molekularbiologie, Auf der Morgenstelle 15, 72076 Tübingen, Germany. E-mail: [email protected].
Present address: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
Present address: Department of Physiology, Biocenter, University of Basel, 4056 Basel, Switzerland.
Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved March 16, 2005

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    Neuronal migration in the murine rostral migratory stream requires serum response factor
    Proceedings of the National Academy of Sciences
    • Vol. 102
    • No. 17
    • pp. 5899-6238

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