title: Pten regulates collective cell migration during specification of the anterior-posterior axis of the mouse embryo.
abstract: Pten, the potent tumor suppressor, is a lipid phosphatase that is best known as a regulator of cell proliferation and cell survival. Here we show that mouse embryos that lack Pten have a striking set of morphogenetic defects, including the failure to correctly specify the anterior-posterior body axis, that are not caused by changes in proliferation or cell death. The majority of Pten null embryos express markers of the primitive streak at ectopic locations around the embryonic circumference, rather than at a single site at the posterior of the embryo. Epiblast-specific deletion shows that Pten is not required in the cells of the primitive streak; instead, Pten is required for normal migration of cells of the Anterior Visceral Endoderm (AVE), an extraembryonic organizer that controls the position of the streak. Cells of the wild-type AVE migrate within the visceral endoderm epithelium from the distal tip of the embryo to a position adjacent to the extraembryonic region. In all Pten null mutants, AVE cells move a reduced distance and disperse in random directions, instead of moving as a coordinated group to the anterior of the embryo. Aberrant AVE migration is associated with the formation of ectopic F-actin foci, which indicates that absence of Pten disrupts the actin-based migration of these cells. After the initiation of gastrulation, embryos that lack Pten in the epiblast show defects in the migration of mesoderm and/or endoderm. The findings suggest that Pten has an essential and general role in the control of mammalian collective cell migration.
authors.affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Bloomekatz
authors.forename: Joaquim
authors.initials: J
authors.lastname: Grego-Bessa
authors.forename: Isabelle
authors.initials: I
authors.lastname: Migeotte
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Anderson
mesh_terms: D000818:Animals; D019521:Body Patterning; D002465:Cell Movement / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology*; D004707:Endoderm / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy
chemical_list: D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse