Towards the molecular biology of cell adhesion in Drosophila.

The characterization of extracellular matrix molecules and their putative receptors is rapidly evolving in Drosophila. Where corresponding vertebrate and Drosophila extracellular proteins have been identified they are very similar with respect to their structural properties, suggesting a high degree of conservation during evolution. By contrast, indications for components homologous to vertebrate cell-cell adhesion molecules are still very sparse. Studies on the regulation of the Drosophila genes encoding cell adhesion molecules that are involved in general basic functions during morphogenesis, together with a knowledge of the function of the genes responsible for pattern formation, should lead towards a more complete understanding of the organism's developmental program.

Drosophila fibronectin: a protein that shares properties similar to those of its mammalian homologue.

This is the first report on the existence in Drosophila of a protein with properties similar to those of vertebrate fibronectin that we shall refer to as Drosophila fibronectin. Rabbit antibodies against human plasma fibronectin have allowed the detection of this molecule in Drosophila haemolymph; common epitopes are shared by the two proteins. Drosophila fibronectin with a subunit mol. wt of approximately 230 kd is a glycoprotein which binds to denatured mammalian collagen. It is present throughout development and is as abundant in embryos as in larvae and adult flies. Drosophila fibronectin is differentially expressed during embryogenesis, a small amount being present before the blastoderm stage. Its concentration increases at gastrulation and reaches a steady-state value at the end of organogenesis. Drosophila fibronectin is predominantly detected by immunofluorescence on frozen sections of 16 h embryos in the extracellular spaces lying between the different tissues and organs. In mature third instar larvae, most of the staining is concentrated in fat body and imaginal discs, and the pattern strongly supports an extracellular localization of the protein. In addition, it is shown that Drosophila embryonic cells can functionally utilize vertebrate fibronectin for their spreading and differentiation. Finally, injection of antihuman plasma fibronectin antibodies in early embryos leads to the same phenotype as injection of Arg-Gly-Asp-containing peptides. This result suggests that one of the Arg-Gly-Asp-bearing protein(s) involved in gastrulation might be fibronectin.

Peptides containing the cell-attachment recognition signal Arg-Gly-Asp prevent gastrulation in Drosophila embryos.

It has recently been suggested that the Arg-Gly-Asp sequence (RGD) forms part of a widespread cell-extracellular matrix recognition system. Analysis of the cell binding sites of vertebrate fibronectin and other extracellular proteins that interact with cell surfaces implicate the same amino acid triplet. Peptides containing this sequence inhibit certain developmental events such as cell-matrix adhesion or cellular migration in vitro and in vivo. The RGD-sequence is also part of the cellular recognition site of the aggregation protein discoidin I in Dictyostelium suggesting that the RGD-recognition system could be universally used. In Drosophila, despite its advanced genetics, very little is known about the extracellular components that are involved in cell movements and morphogenesis. We report here that peptides containing the RGD-sequence prevent gastrulation of Drosophila embryos. The phenotypic effect is similar to that observed in the dorsal-group mutants: no ventral furrow is formed and the embryos lack dorsal-ventral polarity. The specificity of the inhibiting action suggests that the RGD-sequence may also be used by invertebrates to mediate cell-attachment phenomena.