How are neuron patterning and connectivity defined?

During differentiation, neurons generate stereotyped patterns of dendrite and axon arbor connectivity that are critical for the collection, computation, and output of information by the cell. These connectivity patterns are genetically encoded. By using Drosophila sensory neuron arrays as model systems, in particular the somatosensory system, members of our lab have reported a series of important findings, describing how transcription factor codes specify these patterns and how these codes are decoded into circuit construction by control over the timing and amplitude dynamics of effector gene induction. By this process, we can begin to reveal what are the regulatory ‘operations’ that shape the trajectory of a neuron differentiation program. For more reading about this, please see Yun-Jin’s review (Pai and Moore; 2021).

How is arbor pattern and connectivity built, and how is this process controlled?

Neuron differentiation is a sequential process; early events influence the parameters of later ones and different sequences or durations of cell behaviors lead to different outcomes of dendrite and axon arbor connectivity. Therefore, stereotyped dendrite and axonal connectivity patterns emerge out of the progression of differentiation processes. For more reading about this, please see Li-Foongs’ review (Yoong et al, 2019). To address the dynamics of the dendrite arbor differentiation process, we developed a long-term in vivo imaging approach and coupled this in vivo imaging with machine learning-based computer vision techniques to quantify dynamic changes in morphological parameters during differentiation. Overall, we created a powerful pipeline to dissect the operation of effector programs in dendrite arbor differentiation, and we can link final arbor wiring features to the output of local cytoskeletal organization events, even when these occur much earlier in the differentiation process. Through these approaches, we recently showed how the timing and competition between distinct microtubule generation machineries within a dendrite arbor shape its differentiation trajectory. For more reading about this, please see Ollie’s review (Wilkes and Moore, 2020).

Towards an understanding of human neurological disease

Dendrites and axons must also regrow during nervous system regeneration, and microtubule upregulation contributes to synaptic plasticity processes. Where appropriate, we are transitioning our mechanistic findings from Drosophila to look at conservation and investigate therapeutic potential in mouse and human iPSC-derived neurons.

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