Cyclooxygenase-1-derived PGE2 promotes cell motility via the G-protein-coupled EP4 receptor during vertebrate gastrulation.
Gastrulation is a fundamental process during embryogenesis that shapes proper body architecture and establishes three germ layers through coordinated cellular actions of proliferation, fate specification, and movement. Although many molecular pathways involved in the specification of cell fate and polarity during vertebrate gastrulation have been identified, little is known of the signaling that imparts cell motility. Here we show that prostaglandin E(2) (PGE(2)) production by microsomal PGE(2) synthase (Ptges) is essential for gastrulation movements in zebrafish. Furthermore, PGE(2) signaling regulates morphogenetic movements of convergence and extension as well as epiboly through the G-protein-coupled PGE(2) receptor (EP4) via phosphatidylinositol 3-kinase (PI3K)/Akt. EP4 signaling is not required for proper cell shape or persistence of migration, but rather it promotes optimal cell migration speed during gastrulation. This work demonstrates a critical requirement of PGE(2) signaling in promoting cell motility through the COX-1-Ptges-EP4 pathway, a previously unrecognized role for this biologically active lipid in early animal development.
Cha
Yong I
YI
Department of Medicine and Cancer Biology, Cell and Developmental Biology, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-2279, USA.
Kim
Seok-Hyung
SH
Sepich
Diane
D
Buchanan
F Gregory
FG
Solnica-Krezel
Lilianna
L
DuBois
Raymond N
RN
D000818:Animals; D002465:Cell Movement; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000502:physiology*; D015232:Dinoprostone / Q000378:metabolism / Q000502:physiology*; D005775:Gastrula / Q000502:physiology*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology / Q000502:physiology*; D029961:Zebrafish Proteins
D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D029961:Zebrafish Proteins; D051545:Cyclooxygenase 1; D019869:Phosphatidylinositol 3-Kinases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605872:ptges protein, zebrafish; D015232:Dinoprostone