Journal article
Prostaglandin G beta gamma signaling stimulates gastrulation movements by limiting cell adhesion through Snai1a stabilization
Development (Cambridge), Vol.137(8), pp.1327-1337
04/15/2010
DOI: 10.1242/dev.045971
PMCID: PMC2847468
PMID: 20332150
Abstract
Gastrulation movements form the germ layers and shape them into the vertebrate body. Gastrulation entails a variety of cell behaviors, including directed cell migration and cell delamination, which are also involved in other physiological and pathological processes, such as cancer metastasis. Decreased Prostaglandin E(2) (PGE(2)) synthesis due to interference with the Cyclooxygenase (Cox) and Prostaglandin E synthase (Ptges) enzymes halts gastrulation and limits cancer cell invasiveness, but how PGE(2) regulates cell motility remains unclear. Here we show that PGE(2)-deficient zebrafish embryos, impaired in the epiboly, internalization, convergence and extension gastrulation movements, exhibit markedly increased cell-cell adhesion, which contributes to defective cell movements in the gastrula. Our analyses reveal that PGE(2) promotes cell protrusive activity and limits cell adhesion by modulating E-cadherin transcript and protein, in part through stabilization of the Snai1a (also known as Snail1) transcriptional repressor, an evolutionarily conserved regulator of cell delamination and directed migration. We delineate a pathway whereby PGE(2) potentiates interaction between the receptor-coupled G protein beta gamma subunits and Gsk3 beta to inhibit proteasomal degradation of Snai1a. However, overexpression of beta-catenin cannot stabilize Snai1a in PGE(2)-deficient gastrulae. Thus, the Gsk3 beta-mediated and beta-catenin-independent inhibition of cell adhesion by Prostaglandins provides an additional mechanism for the functional interactions between the PGE(2) and Wnt signaling pathways during development and disease. We propose that ubiquitously expressed PGE(2) synthesizing enzymes, by promoting the stability of Snai1a, enable the precise and rapid regulation of cell adhesion that is required for the dynamic cell behaviors that drive various gastrulation movements.
Details
- Title: Subtitle
- Prostaglandin G beta gamma signaling stimulates gastrulation movements by limiting cell adhesion through Snai1a stabilization
- Creators
- Christina K. Speirs - Vanderbilt UniversityKristin K. Jernigan - Vanderbilt UniversitySeok-Hyung Kim - Vanderbilt UniversityYong I. Cha - Vanderbilt UniversityFang Lin - University of IowaDiane S. Sepich - Vanderbilt UniversityRaymond N. DuBois - The University of Texas MD Anderson Cancer CenterEthan Lee - Vanderbilt UniversityLilianna Solnica-Krezel - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- Development (Cambridge), Vol.137(8), pp.1327-1337
- DOI
- 10.1242/dev.045971
- PMID
- 20332150
- PMCID
- PMC2847468
- NLM abbreviation
- Development
- ISSN
- 0950-1991
- eISSN
- 1477-9129
- Publisher
- COMPANY OF BIOLOGISTS LTD
- Number of pages
- 11
- Grant note
- 1S10RR015682; GM77770 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA S10RR015682 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) R01GM077770 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Language
- English
- Date published
- 04/15/2010
- Academic Unit
- Anatomy and Cell Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984284348102771
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