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PubMed · 9799237

Serum response factor is essential for mesoderm formation during mouse embryogenesis.

S Arsenian·B Weinhold·M Oelgeschläger·U Rüther·A Nordheim
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Abstract

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.

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AnimalsCalcium-Calmodulin-Dependent Protein KinasesCell DivisionDNA-Binding ProteinsEmbryonic and Fetal DevelopmentGene Expression Regulation, DevelopmentalGene TargetingGenes, Immediate-EarlyGenetic MarkersGenotypeHistocytochemistryImmunohistochemistryMesodermMiceMice, KnockoutMutationNuclear ProteinsRNA, MessengerSerum Response FactorSignal TransductionStem CellsTranscription, GeneticJournal ArticleResearch Support, Non-U.S. Gov't

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S Arsenian, B Weinhold, M Oelgeschläger, U Rüther, A Nordheim. 1998-11-02. Serum response factor is essential for mesoderm formation during mouse embryogenesis.. https://doi.org/10.1093/emboj%2F17.21.6289

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