| First Author | Weinhold B | Year | 2000 |
| Journal | EMBO J | Volume | 19 |
| Issue | 21 | Pages | 5835-44 |
| PubMed ID | 11060034 | Mgi Jnum | J:65669 |
| Mgi Id | MGI:1927031 | Doi | 10.1093/emboj/19.21.5835 |
| Citation | Weinhold B, et al. (2000) Srf(-/-) ES cells display non-cell-autonomous impairment in mesodermal differentiation. EMBO J 19(21):5835-44 |
| abstractText | The serum response factor (SRF) transcription factor is essential for murine embryogenesis. SRF:(-/-) embryos stop developing at the onset of gastrulation, lacking detectable mesoderm. This developmental defect may reflect cell-autonomous impairment of SRF:(-/-) embryonic cells in mesoderm formation. Alternatively, it may be caused by a non-cell-autonomous defect superimposed upon inappropriate provision of mesoderm-inducing signals to primitive ectodermal cells. We demonstrate that the ability of SRF:(-/-) embryonic stem (ES) cells to differentiate in vitro into mesodermal cells is indeed impaired. However, this impairment can be modulated by external, cell-independent factors. Retinoic acid, but not dimethylsulfoxide, permitted activation of the mesodermal marker gene T(Bra), which was also activated when SRF was expressed in SRF:(-/-) ES cells. Embryoid bodies from SRF:(-/-) ES cell aggregates also activated mesodermal marker genes, but displayed unusual morphologies and impairment in cavitation. Finally, in nude mice, Srf(-/-) ES cells readily differentiated into mesodermal cells of SRF:(-/-) genotype, including cartilage, bone or muscle cells. We demonstrate that SRF contributes to mesodermal gene expression of ES cells and that SRF:(-/-) ES cells display a non-cell-autonomous defect in differentiation towards mesoderm. |
