title: β-Pix directs collective migration of anterior visceral endoderm cells in the early mouse embryo.
abstract: Collective epithelial migration is important throughout embryonic development. The underlying mechanisms are poorly understood but likely involve spatially localized activation of Rho GTPases. We previously reported that Rac1 is essential for generating the protrusive activity that drives the collective migration of anterior visceral endoderm (AVE) cells in the early mouse embryo. To identify potential regulators of Rac1, we first performed an RNAi screen of Rho family exchange factors (guanine nucleotide exchange factor [GEF]) in an in vitro collective epithelial migration assay and identified β-Pix. Genetic deletion of β-Pix in mice disrupts collective AVE migration, while high-resolution live imaging revealed that this is associated with randomly directed protrusive activity. We conclude that β-Pix controls the spatial localization of Rac1 activity to drive collective AVE migration at a critical stage in mouse development.
authors.affiliation: Cell Biology Program, omelchet@mskcc.org halla@mskcc.org.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Omelchenko
authors.affiliation: Cell Biology Program.
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Rabadan
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Rocío
authors.initials: R
authors.lastname: Hernández-Martínez
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Grego-Bessa
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Anderson
authors.affiliation: Cell Biology Program, omelchet@mskcc.org halla@mskcc.org.
authors.forename: Alan
authors.initials: A
authors.lastname: Hall
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D004622:Embryo, Mammalian; D004707:Endoderm / Q000166:cytology*; D004847:Epithelial Cells / Q000166:cytology; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D064067:Rho Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D014781:Viscera / Q000166:cytology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D009479:Neuropeptides; C484602:Rac1 protein, mouse; D064067:Rho Guanine Nucleotide Exchange Factors; D020830:rac1 GTP-Binding Protein
keywords: AVE migration; GEFs; Rho GTPases; anterior–posterior axis; collective cell migration; mouse embryo