Reducing the expression of the Numb adaptor protein in neurons increases the searching behavior of Drosophila larvae.

Drosophila larval crawling is easily-observable and relatively stereotyped. Crawling consists of linear locomotion interrupted by periods when the larvae pause, swing their heads, and change direction (a 'search'). Here we identify Numb, a peripheral membrane adaptor protein, as an important regulator of searching behavior. When Numb RNAi transgenes were expressed in all neurons, searching frequency increased while linear movement appeared normal. Numb's role in suppressing searching behavior was verified by rescuing this phenotype with a Numb homologue from mice. Such behavioral specificity suggests that further analysis of searching might help identify additional, evolutionarily-conserved interactors of the Numb protein.