Neuronal migration in the murine rostral migratory stream requires serum response factor.
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.
Alberti
Siegfried
S
Department of Molecular Biology, Institute for Cell Biology, Tübingen University, 72076 Tübingen, Germany.
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
D000199:Actins / Q000502:physiology; D000818:Animals; D001921:Brain / Q000502:physiology*; D002465:Cell Movement; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D016548:Prosencephalon / Q000002:abnormalities / Q000502:physiology; D017384:Sequence Deletion; D026362:Serum Response Factor / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*
D000199:Actins; D026362:Serum Response Factor