Abstract
Dendrite arbor pattern determines the functional characteristics of a neuron. It is founded on primary branch structure, defined through cell intrinsic and transcription-factor-encoded mechanisms. Developing arbors have extensive acentrosomal microtubule dynamics, and here, we report an unexpected role for the atypical actin motor Myo6 in creating primary branch structure by specifying the position, polarity, and targeting of these events. We carried out in vivo time-lapse imaging of Drosophila adult sensory neuron differentiation, integrating machine-learning-based quantification of arbor patterning with molecular-level tracking of cytoskeletal remodeling. This revealed that Myo6 and the transcription factor Knot regulate transient surges of microtubule polymerization at dendrite tips; they drive retrograde extension of an actin filament array that specifies anterograde microtubule polymerization and guides these microtubules to subdivide the tip into multiple branches. Primary branches delineate functional compartments; this tunable branching mechanism is key to define and diversify dendrite arbor compartmentalization.
•Long-term in vivo imaging of dendrite differentiation with automated quantitation•Anterograde-polymerizing microtubules subdivide the dendrite tip to create branches•Actin motor Myosin6 stabilizes filopodia-derived actin tails to guide microtubules•Transcription factor Knot regulates Myosin6 for dendrite arbor diversification
Through in vivo imaging and computer-vision-based screens, Yoong et al. discover the actin motor Myosin6 organizes actin to induce and guide tip-specific anterograde microtubule polymerization events that create primary branches. The transcription factor Knot regulates Myosin6 for neuron diversification.