title: SRF is essential for mesodermal cell migration during elongation of the embryonic body axis.
abstract: Mesoderm formation in the mouse embryo initiates around E6.5 at the primitive streak and continues until the end of axis extension at E12.5. It requires the process of epithelial-to-mesenchymal transition (EMT), wherein cells detach from the epithelium, adopt mesenchymal cell morphology, and gain competence to migrate. It was shown previously that, prior to mesoderm formation, the transcription factor SRF (Serum Response Factor) is essential for the formation of the primitive streak. To elucidate the role of murine Srf in mesoderm formation during axis extension we conditionally inactivated Srf in nascent mesoderm using the T(s)::Cre driver mouse. Defects in mutant embryos became apparent at E8.75 in the heart and in the allantois. From E9.0 onwards body axis elongation was arrested. Using genome-wide expression analysis, combined with SRF occupancy data from ChIP-seq analysis, we identified a set of direct SRF target genes acting in posterior nascent mesoderm which are enriched for transcripts associated with migratory function. We further show that cell migration is impaired in Srf mutant embryos. Thus, the primary role for SRF in the nascent mesoderm during elongation of the embryonic body axis is the activation of a migratory program, which is a prerequisite for axis extension.
authors.affiliation: Max Planck Institute for Molecular Genetics, Department of Developmental Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany; Free University Berlin, Dept. of Biology, Chemistry and Pharmacy, Takustrasse 3, 14195 Berlin, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Schwartz
authors.affiliation: Max Planck Institute for Molecular Genetics, Department of Developmental Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Marks
authors.affiliation: Max Planck Institute for Molecular Genetics, Department of Developmental Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Wittler
authors.affiliation: Max Planck Institute for Molecular Genetics, Department of Developmental Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Werber
authors.affiliation: Max Planck Institute for Molecular Genetics, Department of Developmental Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Währisch
authors.affiliation: Department of Molecular Biology, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Nordheim
authors.affiliation: Max Planck Institute for Molecular Genetics, Department of Developmental Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.
authors.forename: Bernhard G
authors.initials: BG
authors.lastname: Herrmann
authors.affiliation: Max Planck Institute for Molecular Genetics, Department of Developmental Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany. Electronic address: grote@molgen.mpg.de.
authors.forename: Phillip
authors.initials: P
authors.lastname: Grote
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005326:Fetal Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D026362:Serum Response Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D022502:Stress Fibers / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D000098908:Brachyury Protein
chemical_list: D015820:Cadherins; D005326:Fetal Proteins; D026362:Serum Response Factor; D020825:T-Box Domain Proteins; D014746:Vimentin; D000098908:Brachyury Protein
keywords: Body axis elongation; Brachyury; Epithelial–mesenchymal transition; Migration; Mouse embryo; Serum Response Factor (SRF)