Sci. STKE, 10 January 2006
DEVELOPMENT Below the Speed Limit in the Absence of PGE2
Prostaglandins had been implicated in early development, and in zebrafish loss of cyclooxygenase 1 (COX-1) caused gastrulation defects. Cha et al. now show that signaling mediated by the production of prostaglandin E2 (PGE2) is responsible for the embryonic defects. Transcripts for PGE2 synthase (Ptges in zebrafish) and COX-1 were expressed at the same time and places during gastrulation. Furthermore, PGE2 was detected by mass spectrometry during gastrulation. Injection of antisense morpholino oligonucleotides against Ptges caused gastrulation defects consistent with aberrant cell movement without affecting patterning or cell fate specification (based on marker analysis). Only exogenous PGE2, not PGI2 or PGF2α, rescued the Ptges-deficient embryos. Sequence searching revealed two candidate zebrafish PGE2 receptors, EP2 and EP4, of which only EP4 was present during gastrulation. Injection of antisense morpholino oligonucleotides against EP4 caused gastrulation defects like those observed for loss of COX-1 or Ptges. Time-lapse microscopy revealed that the EP4-deficient cells moved more slowly, but in the proper direction. Finally, analysis of the phosphorylation state of Akt and extracellular signal-regulated kinase (ERK) indicated that EP4 was coupled to a phosphoinositide 3-kinase (PI3K) to Akt pathway. Thus, PGE2 appears to play an essential permissive role in gastrulation through its effects on cell migration.
Y. I. Cha, S.-H. Kim, D. Sepich, F. G. Buchanan, L. Solnica-Krezel, R. N. DuBois, Cyclooxygenase-1-derived PGE2 promotes cell motility via the G-protein-coupled EP4 receptor during vertebrate gastrulation. Genes Dev. 20, 77-86 (2006). [Abstract] [Full Text]
Citation: Below the Speed Limit in the Absence of PGE2. Sci. STKE 2006, tw469 (2006).
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