Background: During brain development, neurons migrate from germinal zones to their final positions to assemble neural circuits. A unique saltatory cadence involving cyclical organelle movement (e.g., centrosome motility) and leading-process actomyosin enrichment prior to nucleokinesis organizes neuronal migration. While functional evidence suggests that leading-process actomyosin is essential for centrosome motility, the role of the actin-enriched leading process in globally organizing organelle transport or traction forces remains unexplored.
Results: We show that myosin ii motors and F-actin dynamics are required for Golgi apparatus positioning before nucleokinesis in cerebellar granule neurons (CGNs) migrating along glial fibers. Moreover, we show that primary cilia are motile organelles, localized to the leading-process F-actin-rich domain and immobilized by pharmacological inhibition of myosin ii and F-actin dynamics. Finally, leading process adhesion dynamics are dependent on myosin ii and F-actin.
Conclusions: We propose that actomyosin coordinates the overall polarity of migrating CGNs by controlling asymmetric organelle positioning and cell-cell contacts as these cells move along their glial guides.
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http://dx.doi.org/10.1186/1749-8104-9-26 | DOI Listing |
EMBO J
December 2024
Laboratory of Systems Neurobiology and Medicine, Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara, 630-0192, Japan.
Neurons migrate in a saltatory manner by repeating two distinct steps: extension of the leading process and translocation of the cell body. The former step is critical for determining the migratory route in response to extracellular guidance cues. In the latter step, neurons must generate robust forces that translocate the bulky soma against mechanical barriers of the surrounding three-dimensional environment.
View Article and Find Full Text PDFFront Cell Dev Biol
September 2020
Laboratory of Systems Neurobiology and Medicine, Division of Biological Science, Nara Institute of Science and Technology, Nara, Japan.
To establish and maintain proper brain architecture and elaborate neural networks, neurons undergo massive migration. As a unique feature of their migration, neurons move in a saltatory manner by repeating two distinct steps: extension of the leading process and translocation of the cell body. Neurons must therefore generate forces to extend the leading process as well as to translocate the cell body.
View Article and Find Full Text PDFNeurosci Res
May 2019
Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto, 606-8501, Japan; Graduate School of Biostudies, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto, 606-8501, Japan.
Somal translocation in long bipolar neurons is regulated by actomyosin contractile forces, yet the precise spatiotemporal sites of force generation are unknown. Here we investigate the force dynamics generated during somal translocation using traction force microscopy. Neurons with a short leading process generated a traction force in the growth cone and counteracting forces in the leading and trailing processes.
View Article and Find Full Text PDFAdv Exp Med Biol
November 2017
Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
During development, production of neurons from neural stem cells, migration of neurons from their birthplace to their final location, and extension of neurites, axons, and dendrites are important for the formation of functional neuronal circuits. The actin cytoskeleton has major roles in the morphological development of neurons. In this chapter, we focused on the distribution and function of the actin-binding protein, drebrin, to elucidate the importance of drebrin-bound F-actin in neurons during early developmental stages of neurons in embryonic, postnatal, and adult brains.
View Article and Find Full Text PDFNat Commun
February 2017
Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
Neuronal migration from a germinal zone to a final laminar position is essential for the morphogenesis of neuronal circuits. While it is hypothesized that microtubule-actomyosin crosstalk is required for a neuron's 'two-stroke' nucleokinesis cycle, the molecular mechanisms controlling such crosstalk are not defined. By using the drebrin microtubule-actin crosslinking protein as an entry point into the cerebellar granule neuron system in combination with super-resolution microscopy, we investigate how these cytoskeletal systems interface during migration.
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