Cytoskeletal coordination during neuronal migration.

Discoveries from human and mouse genetics have identified cytoskeletal and signaling proteins that are essential for neuronal migration in the developing brain. To provide a meaningful context for these studies, we took an unbiased approach of correlative electron microscopy of neurons migrating through a three-dimensional matrix, and characterized the cytoskeletal events that occur as migrating neurons initiate saltatory forward movements of the cell nucleus. The formation of a cytoplasmic dilation in the proximal leading process precedes nuclear translocation. Cell nuclei translocate into these dilations in saltatory movements. Time-lapse imaging and pharmacological perturbation suggest that nucleokinesis requires stepwise or hierarchical interactions between microtubules, myosin II, and cell adhesion. We hypothesize that these interactions couple leading process extension to nuclear translocation during neuronal migration.

[1]  Ehud Goldin,et al.  Identification and Characterization of Nonmuscle Myosin II-C, a New Member of the Myosin II Family* , 2004, Journal of Biological Chemistry.

[2]  Donna J. Webb,et al.  Adhesion assembly, disassembly and turnover in migrating cells – over and over and over again , 2002, Nature Cell Biology.

[3]  Roland Eils,et al.  Nuclear Envelope Breakdown Proceeds by Microtubule-Induced Tearing of the Lamina , 2002, Cell.

[4]  Timothy J Mitchison,et al.  Dissecting Temporal and Spatial Control of Cytokinesis with a Myosin II Inhibitor , 2003, Science.

[5]  G. Borisy,et al.  Cell Migration: Integrating Signals from Front to Back , 2003, Science.

[6]  F. Solomon,et al.  Cytochalasin separates microtubule disassembly from loss of asymmetric morphology , 1981, The Journal of cell biology.

[7]  T. Schroer,et al.  Cytoplasmic Dynein as a Facilitator of Nuclear Envelope Breakdown , 2002, Cell.

[8]  Hynek Wichterle,et al.  Direct Evidence for Homotypic, Glia-Independent Neuronal Migration , 1997, Neuron.

[9]  E. Korn,et al.  Blebbistatin and blebbistatin-inactivated myosin II inhibit myosin II-independent processes in Dictyostelium. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  S. Mcconnell,et al.  Tangential migration of neurons in the developing cerebral cortex. , 1995, Development.

[11]  P. Rakić Mode of cell migration to the superficial layers of fetal monkey neocortex , 1972, The Journal of comparative neurology.

[12]  R. Wong,et al.  Ventricle-directed migration in the developing cerebral cortex , 2002, Nature Neuroscience.

[13]  D. Gross,et al.  Antagonistic forces generated by myosin II and cytoplasmic dynein regulate microtubule turnover, movement, and organization in interphase cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[14]  J. C. Edmondson,et al.  Glial-guided granule neuron migration in vitro: a high-resolution time- lapse video microscopic study , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[15]  Torsten Wittmann,et al.  Motor proteins regulate force interactions between microtubules and microfilaments in the axon , 2000, Nature Cell Biology.

[16]  S. Mcconnell,et al.  Postmitotic neurons migrate tangentially in the cortical ventricular zone. , 1997, Development.

[17]  M. Hatten,et al.  New Directions in Neuronal Migration , 2002, Science.

[18]  W. Dobyns,et al.  Lissencephaly and the molecular basis of neuronal migration. , 2003, Human molecular genetics.

[19]  S. Mcconnell,et al.  Doublecortin Microtubule Affinity Is Regulated by a Balance of Kinase and Phosphatase Activity at the Leading Edge of Migrating Neurons , 2004, Neuron.

[20]  Michel Bornens,et al.  Nucleokinesis in Tangentially Migrating Neurons Comprises Two Alternating Phases: Forward Migration of the Golgi/Centrosome Associated with Centrosome Splitting and Myosin Contraction at the Rear , 2005, The Journal of Neuroscience.

[21]  Jaime Grutzendler,et al.  Two modes of radial migration in early development of the cerebral cortex , 2001, Nature Neuroscience.

[22]  Arturo Alvarez-Buylla,et al.  Chain Migration of Neuronal Precursors , 1996, Science.

[23]  C. Mason,et al.  Cytology and neuron-glial apposition of migrating cerebellar granule cells in vitro , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.