Alternative splicing of RNA transcripts has long been recognized as one way of generating molecular diversity. But a recent paper D. Schmucker et al., Cell 101, 1–20, 2000 sets what is surely a new record, with the identification of a Drosophila axon guidance receptor, termed Dscam, that has no fewer than 38,000 different isoforms. The extracellular domain is assembled in modular fashion, with multiple alternatives for each module (see diagram). Although it is possible that not all combinations are expressed in vivo, many clearly are: among 50 randomly selected Dscam cDNAs, 49 were unique.

The authors confirm that Dscam is involved in axon guidance, but whether the isoforms have different functions remains an open question. It is tempting to think that this molecular diversity is somehow related to the complexity of the neural wiring, but how a neuron could make use of so many different possibilities—given the difficulties of specifying the splicing pattern with any precision—is still anyone's guess.

NOTE The page numbering for the article by Schmucker et al. is incorrect. The correct reference is D. Schmucker et al., Cell 101, 671–684, 2000.