Dscam1 Has Diverse Neuron Type-Specific Functions in the Developing CNS.

Two key features endow Down syndrome cell adhesion molecule 1 (Dscam1) with the potential to provide a ubiquitous code for neuronal arbor self-avoidance. First, Dscam1 contains three large cassettes of alternative exons, so that stochastic alternative splicing yields 19,008 Dscam1 isoforms with different Ig ectodomains. Second, each neuron expresses a different subset of Dscam1 isoforms, and isoform-specific homophilic binding causes repulsion. This results in even spacing of self-arbors, while processes of other neurons can intermingle and share the same synaptic partners. In principle, this Dscam1 code could ensure arbor spacing of all neurons in This model is strongly supported by studies on dendrite spacing in the peripheral nervous system and studies on axonal branch segregation during brain development. However, the situation is less clear for central neuron dendrites, the major substrate for synaptic input in the CNS. We systematically tested the role of Dscam1 for dendrite growth and spacing in eight different types of identified central neurons. Knockdown of Dscam1 causes severe dendritic clumping and length reductions in efferent glutamatergic and aminergic neurons. The primary cause for these dendritic phenotypes could be impaired self-avoidance, a growth defect, or both. In peptidergic efferent neurons, many central arbors are not formed, arguing for a growth defect. By contrast, knockdown of Dscam1 does not affect dendrite growth or spacing in any of the five different types of interneurons tested. Axon arbor patterning is not affected in any neuron type tested. We conclude that Dscam1 mediates diverse, neuron type-specific functions during central neuron arbor differentiation.