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Understanding the molecular mechanisms that control elaborate branching patterns of axons and dendrites is central to unraveling how the complex,precise wiring of the adult brain is achieved during development.In the past decade,it has been found that the large isoform diversity of the Drosophila Down Syndrome Cell Adhesion Molecule(Dscam1)and the mouse clustered protocadherins(PCDHs)is important for dendrite self-avoidance.The isoform diversity is thought to provide each neuron with a distinct “surface tag”,thereby endowing individual neurons with unique molecular identities.A canonical model suggests that homophilic binding of identical Dscam1 receptor isoforms on sister dendrites ensures self-avoidance even when just a single isoform is expressed.However,the question of whether this canonical role provides the mechanistic basis of all Dscam1 functions is still open to debate.Addressing this point,we detected a cellintrinsic 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.