Arginylation Regulates Neural Crest Migration Figure 8. Ate1-dependent impairment of cell migration preferentially affects cranial neural crest-dependent morphogenesis. Arginyltransferase Ate1 has been found to arginylate multiple intracellular targets, including a large subset of cytoskeletal proteins and a smaller subset of regulatory proteins. A combination of these arginylation events results in impairment of cell adhesion and the cytoskeletal structures that lead to slower migration speeds. The three migrating subpopulations of Wnt1-expressing cells—cranial neural crest (bright orange-yellow arrows), vagal and sacral neural crest (large pale yellow arrows), and trunk neural crest (pale yellow arrowheads)—are differentially affected by this impaired migration. In the trunk, cells migrating over short distances with relatively slow speeds are apparently capable of getting to their destinations despite the Ate1-dependent defects. Cells of the vagal and sacral neural crest migrate individually along the expanding gut; while they are believed to be the fastest migrating neural crest cells, our data suggest that this migration may be greatly aided by the expanding surrounding tissues and that Ate1- dependent impairments do not affect the final positioning of these cells in the enteric nervous system. Cranial neural crest giving rise to some of the skull bones (top arrow) and palate (bottom arrow) migrate with steady speeds similar to those observed in culture. Migration of these cells is heavily affected by Ate1 knockout, resulting in morphogenic defects in multiple craniofacial structures. doi:10.1371/journal.pgen.1000878.g008 PLoS Genetics | www.plosgenetics.org 11 March 2010 | Volume 6 | Issue 3 | e1000878