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Neuronal migration in the murine rostral migratory stream requires serum response factor.

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 beta-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.

SUBMITTER: Alberti S 

PROVIDER: S-EPMC1087932 | biostudies-literature | 2005 Apr

REPOSITORIES: biostudies-literature

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Neuronal migration in the murine rostral migratory stream requires serum response factor.

Alberti Siegfried S   Krause Sven M SM   Kretz Oliver O   Philippar Ulrike U   Lemberger Thomas T   Casanova Emilio E   Wiebel Franziska F FF   Schwarz Heinz H   Frotscher Michael M   Schütz Günther G   Nordheim Alfred A  

Proceedings of the National Academy of Sciences of the United States of America 20050418 17

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 th  ...[more]