ECTOPIC EXPRESSION OF MYOD1 IN MICE CAUSES PRENATAL LETHALITIES

A variety of differentiated cell types can be converted to skeletal mu scle following transfection with the myogenic regulatory gene MyoD1. T o determine whether MyoD1 is a dominant muscle regulator in vivo, mous e fertilized eggs were microinjected with a beta-actin/MyoD1 gene. Ect opic expression of MyoD1 during mouse embryogenesis led to embryonic l ethalities, the cause of which is not known. Transgenic embryos died b efore midgestation. The majority of tested embryos between 7.5 and 9.5 days, although retarded compared to control littermates, differentiat ed normally into tissues representative of all three germ layers. In m ost 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, demonstra ting the dominant regulatory function of MyoD1 during development. The se 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. (C) 1993 Wiley-Liss, Inc.