Essential role of growth factor receptor‐mediated signal transduction through the mitogen‐activated protein kinase pathway in early embryogenesis of the echinoderm

Abstract

In this study it was shown that growth factor receptors (GFR) play a crucial role in early embryogenesis of the echinoderms Hemicentrotus pulcherrimus and Clypeaster japonicus by transmitting signals to the mitogen-activated protein kinase (MAPK) pathway. The phosphorylation ratio of extracellular signal-regulated kinase 1 (ERK1) changed dynamically during early embryogenesis and showed a peak at the swimming blastula (sBl) stage. Suramin, an inhibitor of GFR, when applied during the sBl stage perturbed morphogenesis, including primary mesenchyme cell (PMC) migration, cell proliferation, archenteron elongation, spiculogenesis, pigment cell differentiation and phosphorylation of myosin light chains (MLC). Genistein, a receptor-type protein tyrosine kinase inhibitor, severely inhibited PMC migration, gastrulation and the phosphorylation of MLC. Manumycin A, a Ras inhibitor, inhibited spiculogenesis and invagination. PD98059, a MAPK/ERK kinase inhibitor, perturbed early PMC migration and pigment cell differentiation, but not spiculogenesis and gastrulation (although these two events were significantly delayed). PMC ingression was not perturbed by genistein, suramin, manumycin A or PD98059. All of the inhibitors perturbed the phosphorylation of ERK1, which was completely restored by exogenous platelet-derived growth factor (PDGF)-AB. PDGF-AB also partially restored elongation of the archenteron by restoring cell proliferation that had been perturbed by suramin.

FGF signals guide migration of mesenchymal cells, control skeletal morphogenesis and regulate gastrulation during sea urchin development

“…Our finding that FGF signaling is crucially required for gastrulation is in line with previous observations showing that FGFR1 is expressed at high levels in the vegetal pole region before and during gastrulation (Lapraz et al, 2006). It is also consistent with previous findings showing that treatments with the growth factor inhibitor suramin severely interfere with gastrulation when applied during blastula stages onward (Katow and Aizu, 2002) and that MEK inhibition by U0126 causes exogastrulation in the Strongylocentrotus (FernandezSerra et al, 2004;Kumano and Foltz, 2003). However, FGFA is probably not the only FGF ligand involved in the regulation of gastrulation, as its inhibition does not eliminate expression of sprouty and pea3 within the vegetal plate and archenteron.…”

A Raf/MEK/ERK signaling pathway is required for development of the sea urchin embryo micromere lineage through phosphorylation of the transcription factor Ets

“…Indeed, a striking phenotype resulted from inhibition of ERK function. In embryos treated with the MEK inhibitor U0126, no PMCs formed, and a much reduced number of SMCs migrated out (Katow and Aizu, 2002). In P. lividus, this inhibitor did not block PMC ingression and differentiation.…”

Mechanisms of the epithelial-to-mesenchymal transition in sea urchin embryos

“…6). 8,116 These previous observations suggest the remote possibility of growth factor involvement in Snail expression in H. pulcherrimus. Thus, apparent Snail-mediated PMC ingression may be regulated by other signaling pathways that consist of integrin-linked kinase and nuclear b-catenin (Figs.…”

“…The MAPK pathway consists of Raf-1, MEK1/2 and ERK1/2 ( Fig. 6), 8,116 and its involvement is predicted by the transient and highly localized activation of ERK in the micromere lineage.…”

“…6). 8,116 Growth factors generate the cytoplasmic signaling cascades including the pathway that upregulates snail through cadherin endocytosis by binding to GFRs. 16,117 Snail is transcribed immediately before PMC ingression at and after the 16-hpf latehatched blastula stage through the 50-hpf early pluteus stage ( Table 2).…”