title: Distinct modes of migration position oligodendrocyte precursors for localized cell division in the developing spinal cord.
abstract: Establishment of the cytoarchitecture of the central nervous system reflects the stereotyped cell migration and proliferation of precursor cells during development. In vitro analyses have provided extensive information on the control of proliferation and differentiation of oligodendrocyte precursors (OPCs), but less is known about the migratory behavior of these cells in vivo. Here we utilize a transgenic mouse line expressing enhanced green fluorescent protein (EGFP) under the proteolipid protein promoter (PLP-EGFP mice) to visualize directly the behaviors of OPCs in developing spinal cord slices. During early development, OPCs disperse from their origin at the ventricular zone by using saltatory migration. This involves orientation of the cell with a leading edge toward the pial surface and alternating stationary and fast-moving phases and dramatic shape changes. Once cells exit the ventricular zone, they exhibit an exploratory mode of migration characterized by persistent translocation without dramatic changes in cell morphology. The control of migration, proliferation, and cytokinesis of OPCs appear to be closely linked. In netrin-1 mutant spinal cords that lack dispersal cues, OPC migration rates were not significantly different, but the trajectories were altered, and numbers of migrating cells were dramatically reduced. In contrast to DNA replication that occurs at the ventricular zone or throughout the spinal cord neuropil, cell division or cytokinesis of OPCs occurs predominantly at the interface between gray and white matters, with the majority of cleavage planes parallel to the pial surface. These studies suggest that positional cues are critical for regulating OPC behavior during spinal cord development.
authors.affiliation: Center for Translational Neuroscience, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Hui-Hsin
authors.initials: HH
authors.lastname: Tsai
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Macklin
authors.forename: Robert H
authors.initials: RH
authors.lastname: Miller
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000235:genetics; D049109:Cell Proliferation; D048430:Cell Shape / Q000235:genetics; D002478:Cells, Cultured; D048749:Cytokinesis / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018991:Myelin Proteolipid Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics; D000075388:Netrin-1; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D018991:Myelin Proteolipid Protein; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000075388:Netrin-1