Dscam1 Is Required for Normal Dendrite Growth and Branching But Not for Dendritic Spacing inDrosophilaMotoneurons

Abstract

Down syndrome cell adhesion molecule, Dscam, serves diverse neurodevelopmental functions, including axon guidance and synaptic adhesion, as well as self-recognition and self-avoidance, depending on the neuron type, brain region, or species under investigation. In Drosophila, the extensive molecular diversity that results from alternative splicing of Dscam1 into Ͼ38,000 isoforms provides neurons with a unique molecular code for self-recognition in the nervous system. Each neuron produces only a small subset of Dscam1 isoforms, and distinct Dscam1 isoforms mediate homophilic interactions, which in turn, result in repulsion and even spacing of self-processes, while allowing contact with neighboring cells. While these mechanisms have been shown to underlie mushroom body development and spacing of mechanosensory neuron dendrites, here we report that Dscam1 plays no role in adult Drosophila motoneuron dendrite spacing, but is required for motoneuron dendritic growth. Targeted expression of Dscam-RNAi in an identified flight motoneuron did not impact dendrite spacing, but instead produced overgrowth. Increasing the knockdown strength severely reduced dendritic growth and branching. Similarly, Dscam mutant motoneurons in an otherwise control background (MARCM) were completely devoid of mature dendrites. These data suggest that Dscam1 is required cell autonomously for normal adult motoneuron dendrite growth in Drosophila. This demonstrates a previously unreported role of Drosophila Dscam1 in central neuron development, and expands the current understanding that Dscam1 operates as a cell adhesion molecule that mediates homophilic repulsion.

Dendrites are dispensable for basic motoneuron function but essential for fine tuning of behavior

“…In 60% of all preparations it abolishes more than 90% of all dendrites and leaves the primary neurite decorated with lamellipodia-like structures (Fig. 1C) (26). In the remaining 40% of all preparations it reduces dendritic length and branching to 50% of controls (26) (see Fig.…”

“…MN5 can be unambiguously identified from animal to animal and displays a stereotyped dendritic morphology comprising a total length of 6,500 μm and >4,000 branches (13). Dendritic architecture is tightly regulated during development by steroid hormones (24), calcium signaling (25), neural activity (19,20), and cell surface signals (26). We have previously shown that the Significance Approximately 100 billion neurons in our brain form 100 trillion synapses onto 100,000 miles of dendritic cable.…”

“…Down syndrome cell adhesion molecule 1, Dscam1, is required cell-intrinsically for normal dendrite formation during development (26). Targeted RNAi knock down of Dscam1 in MN1-5 (Experimental Procedures) always causes one of two distinctly different dendritic defects.…”

“…3B) or by more than 90% (Fig. 3C) (26). In each animal tested, MN5 was first recorded in vivo during tethered flight and then filled intracellularly to determine the degree of dendritic defect.…”

“…We have previously shown (26) that two additional different UAS-Dscam RNAi transgenes yielded similar results (VDRC, fly stock numbers 108835 and 25623). In all experiments UAS-Dcr2 (Bloomington 24650) was coexpressed with UASDscam1 RNAi to enhance transgenic RNAi effects (42) as reported previously (26). As controls, C380-GAL4, UAS-mCD8::GFP;; Cha-GAL80 females were crossed either to UAS-Dcr2 males (control 1 for possible effects of the UASDcr2 construct alone) or to w 1118 males (control 2 for the genetic background for the UAS-RNAi fly lines).…”