Expression pattern of Drosophila ret suggests a common ancestral origin between the metamorphosis precursors in insect endoderm and the vertebrate enteric neurons.

The RET gene, encoding a receptor tyrosine kinase, is unusual among human protooncogenes in that its mutant alleles are implicated in a developmental defect involving enteric neurons as well as in tumorigenesis. The cells affected in both types of disorders are derived from the neural crest. Targeted disruption of mouse ret has revealed an additional role in kidney development. Here we report the analysis of a ret homolog in Drosophila melanogaster, an arthropod with no neural crest. Drosophila ret (D-ret) encodes a protein of 1,235 amino acids that has all of the domains identified in the vertebrate ret, including a cadherin motif. During embryogenesis, D-ret mRNA is first detected in the yolk sac at the late gastrula stage. In the postgastrula, D-ret is expressed in the foregut neurons, excretory system, peripheral ganglia, and the central nervous system. Thus, despite the wide divergence of early embryonic fate maps between vertebrates and invertebrates, D-ret is expressed in cells that are presumed to be the functional equivalents of the ret-expressing cells in vertebrates. Unexpectedly, D-ret is also expressed in the imaginal islands of the endodermal gut. These cells are proliferation-competent precursors for adult midgut that are diffusely embedded in the growth-arrested juvenile gut. These ret-expressing nonneuronal cells are strikingly analogous to vertebrate enteric neurons in their topography, but not in their cell fate. Our finding suggests a previously unrecognized phylogenetic relationship between the ret-expressing cells in vertebrates and the precursor reserves of metamorphosing insects.