Arginylation-dependent neural crest cell migration is essential for mouse development

Satoshi Kurosaka, N. Adrian Leu, Fangliang Zhang, Ralph Bunte, Sougata Saha, Junling Wang, Caiying Guo, Wei He, Anna Kashina

Research output: Contribution to journalArticle

43 Scopus citations

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 prominent defects, including short palate and altered opening to the nasopharynx, and cranial defects that likely contribute to the abnormal breathing and early death. Analysis of neural crest cell movement patterns in situ and cell motility in culture shows an overall delay in the migration of Ate1 knockout cells that is likely regulated by intracellular mechanisms rather than extracellular signaling events. Taken together, our data suggest that arginylation plays a general role in the migration of the neural crest cells in development by regulating the molecular machinery that underlies cell migration through tissues and organs during morphogenesis.

Original languageEnglish (US)
Article numbere1000878
JournalPLoS genetics
Volume6
Issue number3
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Kurosaka, S., Leu, N. A., Zhang, F., Bunte, R., Saha, S., Wang, J., Guo, C., He, W., & Kashina, A. (2010). Arginylation-dependent neural crest cell migration is essential for mouse development. PLoS genetics, 6(3), [e1000878]. https://doi.org/10.1371/journal.pgen.1000878