Ectopic expression of MyoD1 in mice causes prenatal lethalities.
A variety of differentiated cell types can be converted to skeletal muscle following transfection with the myogenic regulatory gene MyoD1. To determine whether MyoD1 is a dominant muscle regulator in vivo, mouse fertilized eggs were microinjected with a beta-actin/MyoD1 gene. Ectopic expression of MyoD1 during mouse embryogenesis led to embryonic lethalities, the cause of which is not known. Transgenic embryos died before midgestation. The majority of tested embryos between 7.5 and 9.5 days, although retarded compared to control littermates, differentiated normally into tissues representative of all three germ layers. In most transgenic embryos there was no indication of myogenic conversion. The expression of the introduced gene was detected in all ectodermal and mesodermal tissues but was absent in all endodermal cells. Forced expression of MyoD1 was associated with the activation of myogenin and MLC2 (but not myf5 or MRF4) genes in non-muscle cell types, demonstrating the dominant regulatory function of MyoD1 during development. These results demonstrate that ectopic MyoD1 expression and activation of myogenin and MLC2 have no significant effects in the determination of cell lineages or the developmental fate of differentiated mesodermal and ectodermal cell lineages.
Institute of Animal Science, ARO, Volcani Center, Bet Dagan, Israel.
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A
Faerman
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S
Pearson-White
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C
Emerson
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M
Shani
D000199:Actins / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D004475:Ectoderm / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005313:Fetal Death / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D017403:In Situ Hybridization; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017570:MyoD Protein / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D018008:Myogenin / Q000235:genetics; D015533:Transcriptional Activation
D000199:Actins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; D018008:Myogenin