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Guiding Neuronal Cell Migrations Downloaded from http://cshperspectives.cshlp.org/ on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Guiding Neuronal Cell Migrations Oscar Marı´n1, Manuel Valiente1, Xuecai Ge2, and Li-Huei Tsai2 1Instituto de Neurociencias, Consejo Superior de Investigaciones Cientı´ficas and Universidad Miguel Herna´ndez, Sant Joan d’Alacant 03550, Spain 2Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Correspondence: [email protected] and [email protected] Neuronal migration is, along with axon guidance, one of the fundamental mechanisms underlying the wiring of the brain. As other organs, the nervous system has acquired the ability to grow both in size and complexity by using migration as a strategy to position cell types from different origins into specific coordinates, allowing for the generation of brain cir- cuitries. Guidance of migrating neurons shares many features with axon guidance, from the use of substrates to the specific cues regulating chemotaxis. There are, however, important differences in the cell biology of these two processes. The most evident case is nucleokinesis, which is an essential component of migration that needs to be integrated within the guidance of the cell. Perhaps more surprisingly,the cellular mechanisms underlying the response of the leading process of migrating cells to guidance cues might be different to those involved in growth cone steering, at least for some neuronal populations. he migration of newly born neurons is a tangentially migrating neurons move in tra- Tprecisely regulated process that is critical jectories that are parallel to the ventricular for the development of brain architecture. Neu- surface and orthogonal to the radial glia rons arise from the proliferative epithelium that palisade (Fig. 1). Besides their relative orienta- covers the ventricular space throughout the neu- tion, some of the basic mechanisms underlying ral tube, an area named the ventricular zone the movement of cells using each of these two (VZ). From there, newly born neurons adopt modes of migration are also different. For exam- two main strategies to disperse throughout the ple, radially migrating neurons often use radial central nervous system (CNS), designated as glial fibers as substrate, whereas tangentially radial and tangential migration (Hatten 1999; migrating neurons do not seem to require their Marı´n and Rubenstein 2003). During radial support to migrate. Even so, neurons may alter- migration, neurons follow a trajectory that is nate from radial to tangential movement and perpendicular to the ventricular surface, mov- vice versa during the course of their migration. ing alongside radial glial fibers expanding This suggests that both types of migrations share the thickness of the neural tube. In contrast, common principles, in particular those directly Editors: Marc Tessier-Lavigne and Alex L. Kolodkin Additional Perspectives on Neuronal Guidance available at www.cshperspectives.org Copyright # 2010 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a001834 Cite this article as Cold Spring Harb Perspect Biol 2010;2:a001834 1 Downloaded from http://cshperspectives.cshlp.org/ on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press O. Marı´n et al. Midbrain Forebrain: Cajal-Retzius cells NCx Projection neurons Forebrain Cortical interneurons LGE Hindbrain PCx Striatal interneurons OB interneurons Oligodendrocytes MGE Hindbrain: Precerebellar neurons LRN (Inferior olive nucleus) OB IO Precerebellar neurons Spinal cord (Lateral reticular nucl.) IML Spinal cord: Oligodendrocytes Sympathetic preganglionic neurons Figure 1. Representative migrations in the developing CNS. Multiple migrations coexist during embryonic development at different areas of the central nervous system. This schema summarizes some of these migrations during the second week of the embryonic period in the mouse. Neurons use tangential and radial migration to reach their final destination; both strategies are used by the same neurons at different stages of development (i.e., cortical interneurons in the forebrain and precerebellar neurons in the hindbrain). (IML) intermediolateral region of the spinal cord; (IO) inferior olive nucleus; (LGE) lateral ganglionic eminence; (LRN) lateral reticular nucleus; (MGE) medial ganglionic eminence; (NCx) neocortex; (OB) olfactory bulb. related to the cell biology of movement (Marı´n the mouse. This primordial layer consists of et al. 2006). Cajal-Retzius cells and the first cohort of pyra- One of the structures that better illustrates midal neurons, which will eventually populate how both types of migrations are integrated dur- the subplate. Cajal-Retzius cells, which play ing brain development isthe cerebral cortex, and important roles during neuronal migration, so we will primarily refer to studies performed arise from discrete pallial sources and colonize on cortical neurons for this review. The adult the entire surface of the cortex through tangen- cerebral cortexcontainstwo main classes of neu- tial migration (Bielle et al. 2005; Takiguchi- rons: glutamatergic cortical projection neurons Hayashi et al. 2004; Yoshida et al. 2006). The (also known as pyramidal cells) and GABAergic next cohort of pyramidal cells forms the cortical interneurons. Pyramidal cells are generated in plate (CP) by intercalating in the preplate and the ventricular zone (VZ) of the embryonic splitting this primitive structure in a superficial pallium—the roof of the telencephalon—and layer, the marginal zone (MZ or layer I), and a reach their final position by radial migration deep layer, the subplate. The development of (Rakic 2007). In contrast, cortical interneurons the neocortex progresses with new waves of neu- are born in the subpallium—the base of telen- rons that occupy progressively more superficial cephalon—and reach the cerebral cortex positions within the CP (Gupta et al. 2002; through a long tangential migration (Corbin Marı´n and Rubenstein 2003). Birth dating stud- et al. 2001; Marı´n and Rubenstein 2001). ies have shown that layers II–VI of the cerebral The earliest cortical neurons form a tran- cortex are generated in an “inside-out” sequence. sient structure known as the preplate, around Neurons generated earlier reside in deeper embryonic day 10 (E10) of gestation age in layers, whereas later-born neurons migrate past 2 Cite this article as Cold Spring Harb Perspect Biol 2010;2:a001834 Downloaded from http://cshperspectives.cshlp.org/ on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Guiding Neuronal Cell Migrations existing layers to form superficial layers which happens during the last cycle of neu- (Angevine and Sidman 1961; Rakic 1974). In rons undergoing locomotion or in early born parallel to this process, GABAergic interneu- pyramidal neurons. This later process, known as rons migrate to the cortex, where they disperse somal translocation, involves nucleokinesis and tangentially via highly stereotyped routes in trailing process remodeling without the extension the MZ, SP, and lower intermediate zone/ of additional leading processes (Miyata et al. subventricular zone (IZ/SVZ) (Lavdas et al. 2001; Miyata and Ogawa 2007; Nadarajah and 1999). Interneurons then switch from tangen- Parnavelas 2002). tial to radial migration to adopt their final lam- inar position in the cerebral cortex (Ang et al. Leading Process Dynamics 2003; Polleux et al. 2002; Tanaka et al. 2003). The leading process acts as the compass of mi- grating neurons, selecting the direction of mi- CELLULAR MECHANISMS IN NEURONAL gration in response to chemotactic cues. The MIGRATION leading process also reflects the state of polariza- Migrating neurons are highly polarized in the tion of migratory neurons, which in some cases direction of their movement. This is achieved may vary in different phases of the migration through the generation, maintenance, and (Fig. 2). For example, newly born pyramidal remodeling of a leading process that marks the cells have a single process as they leave the pallial direction followed by the cell. Leading processes VZ (Noctor et al. 2001), but they become tran- are tipped by structures that are similar to the siently multipolar for a short period of time in growth cones of migrating axons, and as such the SVZ. During this phase, neurons partially are thought to play an important role in sensing generate several short processes oriented the surrounding microenvironment and there- tangentially (Tabata and Nakajima 2003). Sub- by contributing to the guidance of neurons sequently, pyramidal cells become highly polar- (Rakic 1990; Yee et al. 1999). ized again and establish a leading process that The standard movement of neurons is com- remains in contact with radial glial fibers until monly known as locomotion (Nadarajah and they cease migration (Rakic 1972). Parnavelas 2002) (Fig. 2). Neurons undergoing The morphology of the leading process locomotion follow three synchronized steps to varies in different neuronal types, probably move (Ayala et al. 2007; Marı´n and Lo´pez- reflecting an adaptation to different migratory Bendito 2006). First, the cell extends a leading requirements (Fig. 2). In cortical interneurons, process. Second, the nucleus translocates into for instance, the leading process branches as the leading process, a step referred to as nucleo- part of the migratory cycle (Bellion
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