Neuronal Migration in the Developing Cerebral Cortex: Observations Based on Real-time Imaging

Abstract

We have used time-lapse imaging of acute cortical slices to study the migration of neurons from their sites of origin to their positions in the developing neocortex. We found that two distinct modes of cell movement, somal translocation and glia-guided locomotion, are responsible for the radial migration of neurons generated in the cortical ventricular zone. The former is the prevalent form of radial movement of the early-born cortical neurons, while the latter is adopted by those generated later in corticogenesis. Interneurons, found to originate in the ganglionic eminence, follow tangential migratory paths to reach the developing cortex. Upon reaching the cortex, these cells seek the ventricular zone using a mode of movement that we have termed 'ventricle-directed migration', before they migrate to their positions in the cortical plate. In addition to these forms of movement, we report here a unique morphological and migratory behavior for a population of cortical neurons. These cells are multipolar in form, and are highly motile in the formation and retraction of their processes. Based on these morphological features, we refer to this type of cells as 'branching cells' and attribute the phenotype to a subset of cortical interneurons.

Wandering Neuronal Migration in the Postnatal Vertebrate Forebrain

“…As in mammalian cortical migration, the bipolar and multipolar morphologies may also represent two distinct phases of migration, between which young neurons can switch (Nadarajah et al, 2003). Indeed, it was proposed previously that neurons in the canary brain migrated along radial glia for the first few weeks on their way to deep brain regions and then transitioned to a second form of migration independent of radial glia (Alvarez-Buylla and Figure 6.…”

“…Migratory interneurons, derived from the medial and lateral ganglionic eminences, can exhibit multipolar morphology (Nadarajah et al, 2003;Tanaka et al, 2006) and exhibit dynamic branch growth, leading to the formation of new leading processes (Britto et al, 2009;Martini et al, 2009). Time-lapse imaging in vitro has revealed that young cortical interneurons, migrating in the intermediate zone and marginal zone, also move in an undirected, random walk pattern (Tabata and Nakajima, 2003;Tanaka et al, 2009).…”

“…Albeit possible, we think that this scenario is not likely given that the evidence from other systems indicates that most neuronal types studied do not use a single form of migration exclusively. For example, during the course of their journey, neurons in the mammalian cortex (O'Rourke et al, 1992;Nadarajah et al, 2003;Noctor et al, 2004), cerebellum (Köster and Fraser, 2001), and olfactory bulb (Lois et al, 1996;Hu et al, 1996) have been observed to exhibit changes in morphology, polarity, direction, and the migratory scaffold they use. However, it is possible that some of the bipolar cells that we observed may belong to two different populations.…”

Connexin 43 controls the multipolar phase of neuronal migration to the cerebral cortex

“…All prospective cortical pyramidal neurons are generated in either the ventricular (VZ) or subventricular (SVZ) zones and, after their final division, migrate radially to the cortical plate (CP) situated beneath the pial surface (2). Although it has been observed long ago that cells in the SVZ and intermediate zone (IZ) display multiple processes as they choose and translocate between adjacent radial glial fibers (3,4), it has been only until recently possible to study this transient process by live imaging combined with genetic introduction of GFP (5)(6)(7)(8)(9). The newly generated neurons usually undergo transient multipolar transformation before assuming radial migration (8,10).…”

Cullin 5 regulates Dab1 protein levels and neuron positioning during cortical development

“…In some cases, cells migrate long distances and along intricate routes to reach the places where they differentiate. This is the case during development of the mammalian neocortex (Hatten 2002;Marin and Rubenstein 2003;Nadarajah et al 2003;Kriegstein and Noctor 2004). Neuronal progenitor cells, located in the ventricular zone adjacent to the lateral ventricle, give rise to precursors that migrate radially outward through a cell-poor region called the intermediate zone to establish the initial layers of the cortical plate.…”