Cell-intrinsic requirement of Dscam1 isoform diversity for axon collateral formation

The isoform diversity of the Drosophila Dscam1 receptor is important for neuronal self-recognition and self-avoidance. A canonical model suggests that homophilic binding of identical Dscam1 receptor isoforms on sister dendrites ensures self-avoidance even when only a single isoform is expressed. We detected a cell-intrinsic function of Dscam1 that requires the coexpression of multiple isoforms. Manipulation of the Dscam1 isoform pool in single neurons caused severe disruption of collateral formation of mechanosensory axons. Changes in isoform abundance led to dominant dosage-sensitive inhibition of branching. We propose that the ratio of matching to nonmatching isoforms within a cell influences the Dscam1-mediated signaling strength, which in turn controls axon growth and growth cone sprouting. Cell-intrinsic use of surface receptor diversity may be of general importance in regulating axonal branching during brain wiring.