Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2017 Dec 19;114(51):E10928-E10936. doi: 10.1073/pnas.1713535114. Epub 2017 Dec 4.

STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo.

Author information

1
Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065; hisham.bazzi@uk-koeln.de k-anderson@sloankettering.edu.
2
Department of Dermatology and Venereology, University Hospital of Cologne, 50937 Cologne, Germany.
3
Cologne Cluster of Excellence in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
4
Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065.

Abstract

Regulated mesoderm migration is necessary for the proper morphogenesis and organ formation during embryonic development. Cell migration and its dependence on the cytoskeleton and signaling machines have been studied extensively in cultured cells; in contrast, remarkably little is known about the mechanisms that regulate mesoderm cell migration in vivo. Here, we report the identification and characterization of a mouse mutation in striatin-interacting protein 1 (Strip1) that disrupts migration of the mesoderm after the gastrulation epithelial-to-mesenchymal transition (EMT). STRIP1 is a core component of the biochemically defined mammalian striatin-interacting phosphatases and kinase (STRIPAK) complexes that appear to act through regulation of protein phosphatase 2A (PP2A), but their functions in mammals in vivo have not been examined. Strip1-null mutants arrest development at midgestation with profound disruptions in the organization of the mesoderm and its derivatives, including a complete failure of the anterior extension of axial mesoderm. Analysis of cultured mesoderm explants and mouse embryonic fibroblasts from null mutants shows that the mesoderm migration defect is correlated with decreased cell spreading, abnormal focal adhesions, changes in the organization of the actin cytoskeleton, and decreased velocity of cell migration. The results show that STRIPAK complexes are essential for cell migration and tissue morphogenesis in vivo.

KEYWORDS:

PP2A; STRIP1; STRIPAK; cell migration; mouse embryo

PMID:
29203676
PMCID:
PMC5754794
DOI:
10.1073/pnas.1713535114
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center