Dscam Expression Levels Determine Presynaptic Arbor Sizes in Drosophila Sensory Neurons

•Dscam instructs presynaptic arbor growth, independent of ectodomain diversity•Presynaptic arbor sizes strongly correlate with Dscam expression levels•DLK activates Dscam translation to promote presynaptic arbor growth•FMRP suppresses Dscam translation to restrict presynaptic arbor growth

SummaryExpression of the Down syndrome cell-adhesion molecule (Dscam) is increased in the brains of patients with several neurological disorders. Although Dscam is critically involved in many aspects of neuronal development, little is known about either the mechanism that regulates its expression or the functional consequences of dysregulated Dscam expression. Here, we show that Dscam expression levels serve as an instructive code for the size control of presynaptic arbor. Two convergent pathways, involving dual leucine zipper kinase (DLK) and fragile X mental retardation protein (FMRP), control Dscam expression through protein translation. Defects in this regulation of Dscam translation lead to exuberant presynaptic arbor growth in Drosophila somatosensory neurons. Our findings uncover a function of Dscam in presynaptic size control and provide insights into how dysregulated Dscam may contribute to the pathogenesis of neurological disorders.