Related Experiment Videos
Early myotome specification regulates PDGFA expression and axial skeleton development
M D Tallquist1, K E Weismann, M Hellström
1Program in Developmental Biology, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Abstract:
Reciprocal defects in signaling between the myotome and the sclerotome compartments of the somites in PDGFRalpha and Myf5 mutant embryos lead to alterations in the formation of the vertebrae and the ribs. To investigate the significance of these observations, we have examined the role of PDGF signaling in the developing somite. PDGFA ligand expression was not detected in the myotome of Myf5 null mutant embryos and PDGFA promoter activity was regulated by Myf5 in vitro. PDGFA stimulated chondrogenesis in somite micromass cultures as well as in embryos when PDGFA was knocked into the Myf5 locus, resulting in increased vertebral and rib development. PDGFA expression in the myotome was fully restored in embryos in which MyoD has been introduced at the Myf5 locus but to a lesser extent in similar myogenin knock-in embryos. These results underscore the importance of growth factor signaling within the developing somite and suggest an important role for myogenic determination factors in orchestrating normal development of the axial skeleton.
Insights
Platelet-derived growth factor A (PDGFA) signaling is crucial for axial skeleton development. Myogenic factors like Myf5 regulate PDGFA, impacting vertebral and rib formation in developing embryos.
Area of Science:
- Developmental Biology
- Skeletal Biology
- Molecular Genetics
Background:
- Reciprocal signaling defects between myotome and sclerotome compartments in somites affect vertebral and rib formation.
- Previous observations in PDGFRalpha and Myf5 mutant embryos indicated alterations in axial skeleton development.
Purpose of the Study:
- To investigate the role of Platelet-Derived Growth Factor (PDGF) signaling in the developing somite.
- To elucidate the relationship between myogenic determination factors and axial skeleton development.
Main Methods:
- Analysis of PDGFA ligand expression in Myf5 null mutant embryos.
- In vitro assessment of PDGFA promoter activity regulation by Myf5.
- Somite micromass cultures and in vivo knock-in experiments to evaluate PDGFA's effect on chondrogenesis and skeletal development.
- Comparison of PDGFA expression restoration using MyoD and myogenin knock-ins at the Myf5 locus.
Main Results:
- PDGFA ligand expression was absent in the myotome of Myf5 mutant embryos, with Myf5 regulating PDGFA promoter activity.
- Exogenous PDGFA enhanced chondrogenesis and increased vertebral and rib development in both in vitro and in vivo models.
- MyoD knock-in fully restored PDGFA expression in the myotome, while myogenin had a lesser effect.
Conclusions:
- Growth factor signaling, specifically PDGFA, is vital for developing somites and axial skeleton formation.
- Myogenic determination factors, particularly Myf5 and MyoD, play a significant role in orchestrating normal skeletal development through regulation of PDGFA.