Affiliation:
1. Developmental Biology Unit, University Pierre et Marie Curie (Paris 6)and CNRS, Observatoire Océanologique, 06230 Villefranche-sur-Mer,France.
Abstract
During development, cell migration plays an important role in morphogenetic processes. The construction of the skeleton of the sea urchin embryo by a small number of cells, the primary mesenchyme cells (PMCs), offers a remarkable model to study cell migration and its involvement in morphogenesis. During gastrulation, PMCs migrate and become positioned along the ectodermal wall following a stereotypical pattern that determines skeleton morphology. Previous studies have shown that interactions between ectoderm and PMCs regulate several aspects of skeletal morphogenesis, but little is known at the molecular level. Here we show that VEGF signaling between ectoderm and PMCs is crucial in this process. The VEGF receptor (VEGFR) is expressed exclusively in PMCs, whereas VEGF expression is restricted to two small areas of the ectoderm, in front of the positions where the ventrolateral PMC clusters that initiate skeletogenesis will form. Overexpression of VEGF leads to skeletal abnormalities, whereas inhibition of VEGF/VEGFR signaling results in incorrect positioning of the PMCs, downregulation of PMC-specific genes and loss of skeleton. We present evidence that localized VEGF acts as both a guidance cue and a differentiation signal, providing a crucial link between the positioning and differentiation of the migrating PMCs and leading to morphogenesis of the embryonic skeleton.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference62 articles.
1. Amore, G., Yavrouian, R. G., Peterson, K. J., Ransick, A.,McClay, D. R. and Davidson, E. H. (2003). Sp-deadringer, a sea urchin embryo gene required separately in skeletogenic and oral ectoderm gene regulatory networks. Dev. Biol.261, 55-81.
2. Armstrong, N., Hardin, J. and McClay, D. R.(1993). Cell-cell interactions regulate skeleton formation in the sea urchin embryo. Development119,833-840.
3. Benson, S. C., Sucov, H., Stephens, L., Davidson, E. and Wilt,F. (1987). A lineage-specific gene encoding a major matrix protein of the sea urchin embryo spicule. I. Authentification or the cloned gene and its developmental expression. Dev. Biol.120,499-506.
4. Carmeliet, P. and Tessier-Lavigne, M. (2005). Common mechanisms of nerve and blood vessel wiring. Nature436,193-200.
5. Carson, D. D., Farach, M. C., Earles, D. S., Decker, G. L. and Lennartz, W. J. (1985). A monoclonal antibody inhibits calcium accumulation and skeleton formation in cultured embryonic cells of the sea urchin. Cell41,639-648.