Resumo

FLORES CRUZ, María Guadalupe  e  ESCOBAR, Alfonso. Normal neuronal migration. Salud Ment [online]. 2011, vol.34, n.1, pp.61-66. ISSN 0185-3325.

Ontogenesis of both central and peripheral nervous systems depends on basic, molecular and cellular mechanisms of the normal neuronal migration. Any deviation leads to neural malformations. All neural cells and structures derive from the neural ectoderm, which under the influence of the notochord and the molecules Noggin and Chordin, is transformed consecutively into neural plate, neural groove, neural tube and primary vesicles. Of the latter, the most rostral, the prosencephalon, two vesicles are bilaterally generated, the telencephalon and in the middle, the unpaired diencephalons. The telencepahlic vesicles generate the cerebral hemispheres and the lateral ventricles; the latter constitutes the main source of progenitor neuroepithelial cells (NEC) in the subventricular zone. The NEC massively migrates to constitute the cerebral cortex and other hemispheric structures in the telencephalon and diencephalon. The NEC expresses a broad repertory of markers: BLBP, GLAST, vimentin, tenascin, S100|3 and, in primates GFAP; in a sequential order the NEC form the first cortical layer formed by the marginal zone and the subplate. The marginal zone harbors the Cajal-Retzius reelin positive neurons and reelin negative neurons. Reelin, besides signaling stop to migrating neurons, also participates in ordering the cortical layers; it is known that in mutant mice lacking reelin cortical layers are disrupted. Genetic studies indicate that ApoER2, Vldr (both reelin receptors) and Dab1, reelin signaling adaptor protein, enter into a common pathway leading Dab1 to phosphorylation in migrating neurons. Cortical pyramidal neurons generate at germinal zone; interneurons generate both in Vz and SVZ in medial ganglionic eminence and caudal GE. Two types of neuronal migration coexist, radial and tangential. In radial migration, the neurons move perpendicular to marginal zone and radial glia serves as a scaffold to migrating cells; in the tangential way, neurons migrate in parallel to brain surface guided by semaphorins, neuropilins, cell adhesion molecules, neuregulins, chemokines and the slit and robo families of attractant and repellent molecules. The migratory cycle of neurons involves leading process dynamics and somal translocation, which involves the movement of perinuclear material, organelles and nucleus. Leading process stability depends on the microtubular array that links the leading edge of the cell with the soma. The centrosome is a microtubule center to control microtubule polymerization. In radially migrating neurons, the centrosome establishes a link between centrioles and nuclear membrane. The effective neuronal migration is only completed by translocation of the cell soma, which occurs with cytoplasmic dilatation, and then the centrosome and Golgi apparatus approach it, finally nucleus advances to the cytoplasmic dilatation. Movement of centrosome and nucleus depends on integrity of a microtubule network. Most of the microtubules surrounding the nucleus are tyrosinated, making them dynamic; microtubules at the anterior pole of the nucleus, near the centrosome, are acetylated. Once neurons reach their final destination, they need to cancel the migratory program and differentiate. The mechanisms are unknown; possibly early patterns of activity in the target region could influence. Ca²⁺ influx is a proposed mechanism for halting migration.

Palavras-chave : Neuronal migration; cerebral cortex; molecular mechanisms.

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