Serum response factor is essential for mesoderm formation during mouse embryogenesis.
The transcription factor serum response factor (SRF), a phylogenetically conserved nuclear protein, mediates the rapid transcriptional response to extracellular stimuli, e.g. growth and differentiation signals. DNA- protein complexes containing SRF or its homologues function as nuclear targets of the Ras/MAPK signalling network, thereby directing gene activities associated with processes as diverse as pheromone signalling, cell-cycle progression (transitions G0-G1 and G2-M), neuronal synaptic transmission and muscle cell differentiation. So far, the activity of mammalian SRF has been studied exclusively in cultured cells. To study SRF function in a multicellular organism we generated an Srf null allele in mice. SRF-deficient embryos (Srf -/-) have a severe gastrulation defect and do not develop to term. They consist of misfolded ectodermal and endodermal cell layers, do not form a primitive streak or any detectable mesodermal cells and fail to express the developmental marker genes Bra (T), Bmp-2/4 and Shh. Activation of the SRF-regulated immediate early genes Egr-1 and c-fos, as well as the alpha-Actin gene, is severely impaired. Our study identifies SRF as a new and essential regulator of mammalian mesoderm formation. We therefore suggest that in mammals Ras/MAPK signalling contributes to mesoderm induction, as is the case in amphibia.
Arsenian
S
S
Institut für Molekularbiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Weinhold
B
B
Oelgeschläger
M
M
Rüther
U
U
Nordheim
A
A
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018390:Gene Targeting / Q000379:methods; D017781:Genes, Immediate-Early / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006651:Histocytochemistry; D007150:Immunohistochemistry; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D026362:Serum Response Factor; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells; D014158:Transcription, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D009687:Nuclear Proteins; D012333:RNA, Messenger; D026362:Serum Response Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases