[
Trends Genet,
1996]
In the 15 years since they were first discovered, Wnt proteins have emerged as one of the pre-eminent families of signalling molecules in animal development. Everything, from axis specification to kidney development, from the polarity of a mouse limb to the polarity of a nematode cell division, apparently depends one way or another on the activity of these secreted factors. Yet, while the discovery and characterization of Wnt genes has continued apace, progress in discovering how Wnt signals are received and interpreted has been rather less impressive. When confronted with their failure to identify a receptor, Wnt aficionados are quick to point to the notorious difficulty in obtaining soluble forms of these proteins as the principal obstacle to their progress. Recognizing this problem, Roel Nusse took the inspired step of switching to Drosophila to study Wnt signalling. The reasoning was simple: if only a Wnt gene could be discovered in the fly, it should be relatively trivial to use the sophisticated genetics of Drosophila to identify mutations in the reception pathway. Now, some 10 years later, genetic analysis has, indeed, led Nusse and his colleagues to a putative Wnt receptor-but the route has been rather less direct than might originally have been anticipated.