Replacing nonmuscle myosin 2A with myosin 2C1 permits gastrulation but not placenta vascular development in mice.

Three paralogues of nonmuscle myosin 2 (NM 2A, 2B, and 2C) are expressed in mammals, and the heavy chains are the products of three different genes (Myh9, Myh10, and Myh14, respectively). NM 2A and 2B are essential for mouse development, while 2C is not. Studies on NM 2C are limited and the in vivo function of this paralogue is not clear. Using homologous recombination, cDNA encoding nonmuscle myosin heavy chain 2C1 fused with GFP was introduced into the first coding exon of Myh9, replacing NM 2A expression with NM 2C1 expression in mice. In contrast to A- /A- embryos, which die by embryonic day (E) 6.5, AC1*gfp /AC1*gfp embryos survive through E8.5, demonstrating that NM 2C1 can support mouse development beyond gastrulation. At E9.5 and E10.5, however, AC1*gfp /AC1*gfp embryos are developmentally delayed, with abnormalities in placental vascular formation. The defect in vascular formation is confirmed in allantois explants from AC1*gfp /AC1*gfp embryos. Thus, NM 2C1 cannot support normal placental vascular formation. In addition, AC1*gfp /AC1*gfp mouse embryonic fibroblasts (MEFs) migrate rapidly but with impaired persistence and develop smaller, less mature focal adhesions than A+ /A+ MEFs. This is attributed to enhanced NM 2C1 actomyosin stability and different NM 2C1 subcellular localization than in NM 2A.