Size Control in Dendrites
Many degenerative disorders preferentially affect neurons with large axons/dendrites including Purkinje neurons, Betz cells, motoneurons, and sensory neurons. Thus, it’s plausible that defects in growth machinery that contribute to "extreme" neuron growth contribute to pathology in these diseases. To identify factors required for extreme growth in neurons with large dendrite arbors, we conducted a genetic screen for mutations that differentially affected growth in neurons with different sized dendrite arbors. At present, we have characterized one of these mutants in detail. This mutant selectively affects dendrite growth in neurons with large dendrite arbors without affecting growth of the animal overall. This mutant disrupts a putative amino acid transporter, Pathetic (Path), that localizes to the cell surface and endolysosomal compartments in neurons. Although Path is broadly expressed in neurons and non-neuronal cells, mutation of path impinges on nutrient responses and protein homeostasis specifically in neurons with large dendrite arbors, but not in other cells. Path regulates translational capacity in neurons, and we are currently investigating whether Path can be engaged in other cell types to confer robustness on growth control.
Compartmentalization in Dendrite Growth and Patterning
Axons and dendrites contain structurally and functionally distinct sub-compartments. Whereas axon/dendrite compartmentalization can be attributed to neuronal polarization, the developmental origin of sub-compartments in axons and dendrites is less well understood. To identify the developmental bases for compartment-specific growth and patterning in dendrites, we conducted a genetic screen for mutations that affect growth/patterning of discrete dendritic domains in Drosophila somatosensory neurons. From this screen, we identified mutants that selectively affected terminal dendrites, including terminal dendrite position along the proximal/distal axis, and patterning of terminal dendrites, suggesting that distance from the soma and branch type (major or terminal dendrite) are two key pieces of positional information in dendrite patterning.