Cytoskeletal assembly and dynamics during neuronal development
Neurons are highly polarized cells whose structure and function are intimately tied to their microtubule cytoskeleton. As a neuronal precursor transforms into a mature neuron, distinct functional domains emanate from their cell bodies — the axon and the dendrite. This process involves the reshaping of a radial microtubule array in a neuronal precursor into parallel microtubule array of uniform polarity in axons and mixed polarity in dendrites. Distinct microtubule-associated proteins regulate microtubule organization and function in neurons, and mutations in these proteins are linked to human neurodevelopmental disorders. However, the molecular mechanisms that build the unique microtubule architecture in a developing neuron are poorly understood.
Cheerambathur DK, Prevo B, Hattersley N, Lewellyn L, Corbett KD, Oegema K and Desai A. Dephosphorylation of the Ndc80 tail stabilizes kinetochore-microtubule attachments via the Ska complex. Developmental Cell 41, 424-437 (2017).
Cheerambathur DK and Desai A. Linked in: formation and regulation of microtubule attachments during chromosome segregation. Current Opinion in Cell Biology 26, 113-122 (2014).
Cheerambathur DK, Gassmann R, Cook B, Oegema K and Desai A. Crosstalk between microtubule attachment complexes ensures accurate chromosome segregation. Science 342, 1239-1242 (2013).
Neuronal differentiation is tightly linked to cytoskeletal reorganization
The overarching goal of our research is to gain a detailed mechanistic understanding about how neuronal cells assemble and maintain their complex microtubule architecture. We are particularly interested in deciphering how various microtubule regulators contribute to this process. The lab also employs a multidisciplinary approach involving classical genetic methods and state of the art genome editing tools (CRISPR), and high temporal imaging of neuronal development in vivo in C. elegans to manipulate and visualize the dynamic cellular structures within the neuron.