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

Abstract

The sea urchin embryo is emerging as an attractive model to study morphogenetic processes such as directed migration of mesenchyme cells and cell sheet invagination, but surprisingly, few of the genes regulating these processes have yet been characterized. We present evidence that FGFA, the first FGF family member characterized in the sea urchin, regulates directed migration of mesenchyme cells, morphogenesis of the skeleton and gastrulation during early development. We found that at blastula stages, FGFA and a novel putative FGF receptor are expressed in a pattern that prefigures morphogenesis of the skeletogenic mesoderm and that suggests that FGFA is one of the elusive signals that guide migration of primary mesenchyme cells (PMCs). We first show that fgfA expression is correlated with abnormal migration and patterning of the PMCs following treatments that perturb specification of the ectoderm along the oral-aboral and animal-vegetal axes. Specification of the ectoderm initiated by Nodal is required to restrict fgfA to the lateral ectoderm, and in the absence of Nodal, fgfA is expressed ectopically throughout most of the ectoderm. Inhibition of either FGFA, FGFR1 or FGFR2 function severely affects morphogenesis of the skeleton. Furthermore,inhibition of FGFA and FGFR1 signaling dramatically delays invagination of the archenteron, prevents regionalization of the gut and abrogates formation of the stomodeum. We identified several genes acting downstream of fgfAin these processes, including the transcription factors pea3 and pax2/5/8 and the signaling molecule sprouty in the lateral ectoderm and SM30 and SM50 in the primary mesenchyme cells. This study identifies the FGF signaling pathway as an essential regulator of gastrulation and directed cell migration in the sea urchin embryo and as a key player in the gene regulatory network directing morphogenesis of the skeleton.

Toxicity mechanisms of ionic silver and polymer-coated silver nanoparticles with interactions of functionalized carbon nanotubes on early development stages of sea urchin

“…Growth sp. (Röttinger et al, 2008). It is also known that PMCs remain as a disorganized cell 698 population without cellular extensions near the vegetal pole when inhibitors disrupt 699 FGFA signaling.…”

Par6 regulates skeletogenesis and gut differentiation in sea urchin larvae

“…Duloquin et al (2007) demonstrated that localized VEGF acts as both a guidance cue for the formation of ventrolateral PMC clusters and a signal for the differentiation of skeletogenic cells. On the other hand, Röttinger et al (2008) showed that FGF signaling plays an essential role in the guidance of PMC migration and the direction of skeletal morphogenesis. However, defects in skeletogenesis induced by Mpar6 injection were unlikely due to either the loss of skeletogenic cell differentiation or a lack of ectodermal guidance/direction cues required for skeletogenesis, since in Mpar6 embryos, mesenchyme cells expressed the PMC-specific P4 antigen ( Fig.…”

“…3j; Shimizu et al 1988) and VEGF/FGF-dependent skeletogenic genes, such as sm50 and sm30 (Fig. 3a,m;Duloquin et al 2007;Röttinger et al 2008), and because their descendants expressing the B2C2 antigen ( Fig. 3l; Leaf et al 1987) were allocated on the inner ectoderm wall in a pattern that prefigures the rod branching patterns, i.e., the anterolateral, transverse, postoral, and body rods (Fig.…”

“…Skeletogenesis in sea urchin larvae is controlled by both PMCs and ectodermal cells (Armstrong et al 1993;Ettensohn and Marinda 1993;Guss and Ettensohn 1997;Hardin and Armstrong 1997;Duloquin et al 2007;Röttinger et al 2008). On the other hand, Hamada and Kiyomoto (2003) demonstrated that unidentified signals from PMCs regulate gut differentiation.…”

Functional evolution of Ets in echinoderms with focus on the evolution of echinoderm larval skeletons

“…Echinopluteus and ophiopluteus are similar not only in the presence of the larval skeleton, but also in the shape of the skeleton. The shape of the skeleton is achieved by interaction with the epidermis (Kinoshita and Okazaki 1984;Armstrong et al 1993;Di Bernardo et al 1999;Duloquin et al 2007;Röttinger et al 2008). Some common feature may exist in the larval epidermis of echinoderms that led to a similar interaction with the skeletogenic mesenchyme cells.…”