Cell polarity is critical for various cellular processes including establishing the antero-posterior axis, generating distinct membrane specializations (apical and basal polarity), as well as asymmetric cell division and axon specification. Essentially, cell polarity plays fundamental roles in helping to organize and integrate complex molecular signals in order for cells to make decisions concerning fate, orientation, differentiation, and interaction. In the nervous system, neurons and glia share a mutual dependence in establishing a functional relationship, and none is more evident than the process by which glia form myelin around axons. The formation of myelin is an exquisite example of cell-cell interaction, which consists of the polarized or unidirectional wrapping of multiple layers of membrane concentrically around an axon initiated at the site of the axon-glial interface. While myelination is a highly polarized process, the involvement of cell polarity in its formation remain largely uncharacterized. We have recently identified a novel role for the Par (partitioning defective) polarity complex in the initiation of myelination. This polarity complex localizes asymmetrically in myelin- forming cells at the SC-axon interface, and disruption of Par localization, dramatically inhibits myelination without affecting cell division, migration, or even axonal alignment. The central hypothesis of this proposal is that axonal signals facilitate the breaking of symmetry in the SC and initiate myelination by coordinating cytoskeletal dynamics/rearrangement and gene expression. Our recent findings provide us with a rare opportunity to characterize the presence of this polarized molecular scaffold at the SC-axon interface that leads to the unidirectional activation of myelination. A clear understanding of the molecular and cellular events that pave the way for the myelin-forming cell is vital in advancing therapies for demyelinating diseases such as Multiple Sclerosis, the peripheral neuropathies, and even nerve injury.
Myelination is an exquisite and dynamic example of cell-cell interaction, which requires a series of highly orchestrated events that balance both extrinsic and intrinsic mechanisms to coordinate the spatiotemporal regulation. Demyelination as a result of disease or injury severely disrupts the efficient transmission of the action potential, ultimately resulting in a loss of function. In order to effectively treat these devastating conditions, it is essential to expand our knowledge concerning the generation and maturation of the myelin- forming cells and the processes that lead to myelination.
|Domingues, Helena S; Cruz, Andrea; Chan, Jonah R et al. (2018) Mechanical plasticity during oligodendrocyte differentiation and myelination. Glia 66:5-14|
|Wang, Fei; Yang, Yu-Jian; Yang, Nian et al. (2018) Enhancing Oligodendrocyte Myelination Rescues Synaptic Loss and Improves Functional Recovery after Chronic Hypoxia. Neuron 99:689-701.e5|
|Jiang, Minqing; Rao, Rohit; Wang, Jincheng et al. (2018) The TSC1-mTOR-PLK axis regulates the homeostatic switch from Schwann cell proliferation to myelination in a stage-specific manner. Glia 66:1947-1959|
|Pease-Raissi, Sarah E; Chan, Jonah R (2018) Micro(glial)-managing executive function: white matter inflammation drives catatonia. J Clin Invest 128:564-566|
|Mayoral, Sonia R; Etxeberria, Ainhoa; Shen, Yun-An A et al. (2018) Initiation of CNS Myelination in the Optic Nerve Is Dependent on Axon Caliber. Cell Rep 25:544-550.e3|
|Petersen, Mark A; Ryu, Jae Kyu; Chang, Kae-Jiun et al. (2017) Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage. Neuron 96:1003-1012.e7|
|Pan, Simon; Chan, Jonah R (2017) Regulation and dysregulation of axon infrastructure by myelinating glia. J Cell Biol 216:3903-3916|
|Osso, Lindsay A; Chan, Jonah R (2017) Architecting the myelin landscape. Curr Opin Neurobiol 47:1-7|
|Wu, Lai Man Natalie; Wang, Jincheng; Conidi, Andrea et al. (2016) Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination. Nat Neurosci 19:1060-72|
|Mei, Feng; Mayoral, Sonia R; Nobuta, Hiroko et al. (2016) Identification of the Kappa-Opioid Receptor as a Therapeutic Target for Oligodendrocyte Remyelination. J Neurosci 36:7925-35|
Showing the most recent 10 out of 32 publications