Abstract
The mammalian cerebral cortex contains a high variety of neuronal subtypes that acquire precise spatial locations and form long or short-range connections to establish functional neuronal circuits. During embryonic development, cortical projection neurons are generated in the areas lining the lateral ventricles and they subsequently undergo radial migration to reach the position of their final maturation within the cortical plate. The control of the neuroblast migratory behavior and the coordination of the migration process with other neurogenic events such as cell cycle exit, differentiation and final maturation are crucial to normal brain development. Among the key regulators of cortical neuron migration, the small GTP binding proteins of the Rho family and the atypical Rnd members play important roles in integrating intracellular signaling pathways into changes in cytoskeletal dynamics and motility behavior. Here we review the role of Rnd proteins during cortical neuronal migration and we discuss both the upstream mechanisms that regulate Rnd protein activity and the downstream molecular pathways that mediate Rnd effects on cell cytoskeleton.
Highlights
During the development of the central nervous system, neural progenitors undergo a sequence of distinct cellular events to give rise to the vast array of neurons that populate the entire brain
Excitatory projection neurons, which constitute the majority of cortical neurons, are generated from neural stem/progenitor cells located in the areas lining the lateral ventricles, the ventricular (VZ) and subventricular zones (SVZ) of the dorsal telencephalon (Franco and Muller, 2013; Marin and Muller, 2014)
Newborn neurons usually migrate along the fiber of their mother radial glia, they can jump from one fiber to another during migration, a process that regulates intermixing of neuronal clones within the cortex. This entire process of radial migration can be subdivided into distinct phases (Figure 1C) (Nadarajah and Parnavelas, 2002; Noctor et al, 2004), in which neurons undergo rapid changes in cell polarity, morphology and speed of migration, as they progress from the VZ to the cortical plate (CP)
Summary
During the development of the central nervous system, neural progenitors undergo a sequence of distinct cellular events to give rise to the vast array of neurons that populate the entire brain. It is increasingly evident that a highly motile cellular behavior is crucial for different aspects of cortical neurogenesis, including, but not restricted to radial migration of post-mitotic neurons. The sequential steps of neurogenesis and migration are promoted by the extensive and dynamic remodeling of the cell cytoskeleton. It is the rapid re-organization of the actin filaments and microtubule network that regulates the motility behavior of nuclei in cycling progenitors and of migrating neurons (Lambrechts et al, 2004; Heng et al, 2010; Taverna and Huttner, 2010). Rho proteins act as molecular switches capable of fast cycles of activation and inactivation, which represent an ideal system to regulate the dynamic changes of the cytoskeleton during migration. Rnd in cortical neuron migration nuclear migration and during radial migration of cortical neurons
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