DSCAM is a highly conserved immunoglobulin cell surface receptor that has well characterized roles in axonal guidance, axonal branching and synapse maturation. The DSCAM gene is located on chromosome 21 and has previously been implicated in both neural and cardiac phenotypes in Down syndrome. The authors showed that Dscam RNA is a target of FMRP in Drosophila melanogaster and that comparable (high) levels of Dscam protein are found in flies lacking FMRP or harbouring three copies of the Dscam gene.
To investigate the consequences of increased Dscam protein levels on neuronal wiring, the authors focused on the flies' posterior scutellar (pSc) neurons. Each of these mechanosensory neurons innervates a single bristle on the fly's back and projects into the CNS, forming synapses with specific interneurons. Alterations in their stereotyped and unique arbors can be used as a readout for synaptic targeting errors. Compared with pSc neurons from wild-type flies, in flies lacking FMRP or expressing three copies of the Dscam gene, there was an increase in the number of ectopic branches and an increase in total branch length. Moreover, they exhibited synaptic targeting errors, including misrouting and aberrant midline crossing. These errors were prevented when the levels of Dscam were reduced: in double mutant flies lacking both FMRP and one Dscam allele, the number of axonal targeting errors was substantially reduced.
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