Abstract: As neurons differentiate and assemble into circuits, genetic programs control their complex cellular morphogenesis and connectivity. Disruption of these differentiation processes leads to the complex behavioral phenotypes of neurodevelopmental disorders, and approximately 1 in 54 children develop one or both intellectual disability and autism spectrum disorder. By integrating transcriptomics with in vivo high spatiotemporal resolution time-lapse imaging in Drosophila, we show how genetic programs control the growth and branching dynamics of dendrites by setting the identity, spatial organization, and amplitude of microtubule generation events within the dendrite arbor. Moreover, human genetics is uncovering a large and ever-increasing set of predisposition loci for neurodevelopmental disorders. Therefore, we have developed high-throughput, easy-to-use, automated image quantitation software to study the action of these loci in neuron morphogenesis. We use this to investigate microtubule control as an underlying factor in neurodevelopmental disorders and to highlight new pathways that regulate microtubule generation in differentiating neurons.

Formation, repair, and function of our nervous system requires neuron differentiation—a complex cellular process that occurs over time in an intricate and rapidly changing in vivo environment. My laboratory studies axon and dendrite arbor differentiation and connectivity, a critical process in neuron differentiation and pathology. In particular, dendrite arbor architecture determines the number, distribution, and integration of inputs into the neuron, and it is genetically encoded, being linked to neuron type-specification by transcriptional programs. Many complex neurological disorders are caused through disruption in neuron differentiation processes, to understand how neuron differentiation proceeds and to identify ways we can manipulate it for therapeutic ends is a key biomedical goal; the ultimate objective of my research is to contribute to this mission.