Abstract
Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final target lamina, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating the specific sequential steps of radial neuronal migration in vivo are however still unclear, let alone the effects and interactions with the extracellular environment. In any in vivo context, cells will always be exposed to a complex extracellular environment consisting of (1) secreted factors acting as potential signaling cues, (2) the extracellular matrix, and (3) other cells providing cell–cell interaction through receptors and/or direct physical stimuli. Most studies so far have described and focused mainly on intrinsic cell-autonomous gene functions in neuronal migration but there is accumulating evidence that non-cell-autonomous-, local-, systemic-, and/or whole tissue-wide effects substantially contribute to the regulation of radial neuronal migration. These non-cell-autonomous effects may differentially affect cortical neuron migration in distinct cellular environments. However, the cellular and molecular natures of such non-cell-autonomous mechanisms are mostly unknown. Furthermore, physical forces due to collective migration and/or community effects (i.e., interactions with surrounding cells) may play important roles in neocortical projection neuron migration. In this concise review, we first outline distinct models of non-cell-autonomous interactions of cortical projection neurons along their radial migration trajectory during development. We then summarize experimental assays and platforms that can be utilized to visualize and potentially probe non-cell-autonomous mechanisms. Lastly, we define key questions to address in the future.
Highlights
The mammalian neocortex is built by distinct classes of neurons and glial cells which are organized into six stratified layers
Projection neurons emerge from radial glial cells (RGCs) in the ventricular zone (VZ), intermediate progenitor cells (IPCs), and outer radial glial cells which divide in the subventricular zone (SVZ)
Nascent projection neurons migrate from their place of origin in the VZ/SVZ to their final target position, a process which is highly regulated (Ayala et al, 2007; Valiente and Marín, 2010; Evsyukova et al, 2013)
Summary
The mammalian neocortex is built by distinct classes of neurons and glial cells which are organized into six stratified layers. At around E12, consecutive waves of neurons migrate toward the pial surface and establish the CP by splitting the PP into the two distinct structures: the deeper located subplate (SP) and the superficially positioned marginal zone (MZ) (layer I) (Ayala et al, 2007) (Figure 1A). Studies applying histological and time-lapse imaging techniques have shed some light on the dynamics of the radial migration process and described distinct sequential steps of projection neuron migration (Figure 1A) (Nadarajah et al, 2003; Tabata and Nakajima, 2003; Noctor et al, 2004). Have started to describe and characterize non-cell-autonomous effects and mechanisms in projection neuron migration
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