Regulation of avian cardiogenesis by Fgf8 signaling.
The avian heart develops from paired primordia located in the anterior lateral mesoderm of the early embryo. Previous studies have found that the endoderm adjacent to the cardiac primordia plays an important role in heart specification. The current study provides evidence that fibroblast growth factor (Fgf) signaling contributes to the heart-inducing properties of the endoderm. Fgf8 is expressed in the endoderm adjacent to the precardiac mesoderm. Removal of endoderm results in a rapid downregulation of a subset of cardiac markers, including Nkx2.5 and Mef2c. Expression of these markers can be rescued by supplying exogenous Fgf8. In addition, application of ectopic Fgf8 results in ectopic expression of cardiac markers. Expression of cardiac markers is expanded only in regions where bone morphogenetic protein (Bmp) signaling is also present, suggesting that cardiogenesis occurs in regions exposed to both Fgf and Bmp signaling. Finally, evidence is presented that Fgf8 expression is regulated by particular levels of Bmp signaling. Application of low concentrations of Bmp2 results in ectopic expression of Fgf8, while application of higher concentrations of Bmp2 result in repression of Fgf8 expression. Together, these data indicate that Fgf signaling cooperates with Bmp signaling to regulate early cardiogenesis.
Alsan
Burak H
BH
Molecular Medicine Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Schultheiss
Thomas M
TM
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics; D004707:Endoderm / Q000187:drug effects; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D050991:GATA4 Transcription Factor; D005786:Gene Expression Regulation; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D006609:High Mobility Group Proteins / Q000235:genetics; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D064326:MEF2 Transcription Factors; D008648:Mesoderm / Q000187:drug effects; D009024:Morphogenesis; D009206:Myocardium / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000235:genetics; D055748:SOXB1 Transcription Factors; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D006609:High Mobility Group Proteins; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; C095552:NKX2-5 protein, human; D055748:SOXB1 Transcription Factors; C527788:Sox3 protein, Xenopus; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors