arginylation-dependent neural crest cell migration is essential for mouse developmentarginylation-dependent神经嵴细胞的迁移对鼠标的发展至关重要.pdf

Arginylation-Dependent Neural Crest Cell Migration Is Essential for Mouse Development 1 1 1 2 1 1 Satoshi Kurosaka , N. Adrian Leu , Fangliang Zhang , Ralph Bunte , Sougata Saha , Junling Wang , 3 4 1 Caiying Guo , Wei He , Anna Kashina * 1 Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2 University Laboratory Animal Resources, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 3 Janelia Farm, Ashburn, Virginia, United States of America, 4 Gene Targeting and Transgenic Facility, University of Connecticut Health Center, Farmington, Connecticut, United States of America Abstract Coordinated cell migration during development is crucial for morphogenesis and largely relies on cells of the neural crest lineage that migrate over long distances to give rise to organs and tissues throughout the body. Recent studies of protein arginylation implicated this poorly understood posttranslational modification in the functioning of actin cytoskeleton and in cell migration in culture. Knockout of arginyltransferase (Ate1) in mice leads to embryonic lethality and severe heart defects that are reminiscent of cell migration–dependent phenotypes seen in other mouse models. To test the hypothesis that arginylation regulates cell migration during morphogenesis, we produced Wnt1-Cre Ate1 conditional knockout mice (Wnt1- Ate1), with Ate1 deletion in the neural crest cells driven by Wnt1 promoter. Wnt1-Ate1 mice die at birth and in the first 2–3 weeks after birth with severe breathing problems and with growth and behavioral retardation. Wnt1-Ate1 pups have pro