IngentaConnect Cellular and molecular mechanisms of cerebellar granule cell migr...

Abstract:

The real-time observation of cell movement in brain slice preparations reveals that in the developing brain, postmitotic neurons alter their shape concomitantly with changes in the mode, direction, tempo, and rate of migration as they traverse different cortical layers. Although it has been hypothesized that orchestrated activities of multiple external cues and cell-cell contact are essential for controlling the cortical-layer-specific changes in cell migration, signaling mechanisms and external guidance cues related to the alteration of neuronal cell migration remain to be determined. In this article, we will first review recent studies on position-specific changes in granule cell behavior through different migratory terrains of the developing cerebellar cortex. We will then present possible roles for the coordinated activity of Ca²⁺ channels, NMDA type of glutamate receptors, and intracellular Ca²⁺ fluctuations in controlling cerebellar granule cell movement. Furthermore, we will discuss the crucial roles of brain-derived neurotrophic factor (BDNF), neuregulin (NRG), stromal cell-derived factor 1α (SDF-1α), ephrin-B2, and EphB2 receptor in providing directional cues promoting granule cell migration from the external granular layer (EGL) to the internal granular layer (IGL). Finally, we will demonstrate that endogenous somatostatin controls the migration of granule cells in a cortical layer-specific manner: Endogenous somatostatin accelerates granule cell movement near the birthplace within the EGL, but significantly slows down the movement near their final destination within the IGL.

Keywords: Cerebellar granule cell; neuronal cell migration; N-type Ca2+ channel; NMDA receptor; intracellular Ca2+ levels; BDNF; NRG; SDF-1α, ephrin-B2; somatostatin

Document Type: Research article

DOI: 10.1385/CBB:37:3:213

Affiliations: 1: Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, 44195, Cleveland, OH, 2: Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, 44195, Cleveland, OH, Email: komuroh@ccf.org

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Cellular and molecular mechanisms of cerebellar granule cell migration