In Vitro, Ex Vivo and In Vivo Techniques to Study Neuronal Migration in the Developing Cerebral Cortex (original) (raw)

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

Cerebral Cortex, 2003

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.

Patterns of neuronal migration in the embryonic cortex

Trends in Neurosciences, 2004

Real-time imaging of migrating neurons has changed our understanding of how newborn neurons reach their final positions in the developing cerebral cortex. The migratory routes and modes of migration are more diverse and complex than previously thought. The finding that cortical interneurons migrate to the cortex from origins in the ventral telencephalon has already markedly altered our view of cortical

Auto-attraction of neural precursors and their neuronal progeny impairs neuronal migration

Nature Neuroscience, 2013

nature neuroscience advance online publication B r i e f c o m m u n i c at i o n s Transplantation of neural stem or progenitor cells is an interesting prospect for neuronal replacement in various neurological disorders 1-3 . The efficacy of such transplants will critically depend on efficient migration and integration of donor neurons into the host brain. Neural transplants placed into the adult brain generally form dense clusters at the site of implantation, with only restricted migration of graft-derived neurons into the host brain 4-6 . It has been suggested that migration of transplanted cells might be hampered because the tissue is already fully established, guiding cues are limited and the space is more constricted 7 . In addition, glial scarring at the site of engraftment has been considered to inhibit neuronal migration . We hypothesized that graft-intrinsic interactions between NPCs and their neuronal progeny might interfere with neuronal migration.

A Novel Method of Labeling and Characterizing Migrating Neurons in the Developing Central Nervous System

Experimental Neurology, 2002

Neuronal migration, a discrete event in the developing nervous system, is currently being intensively investigated using a variety of anatomical and molecular approaches. Using 4-chloromethyl benzoyl amino tetramethyl rhodamine (CMTMR) coated particles, we describe here a novel and efficient method of tracer labeling to investigate cell migration in embryonic and postnatal brain. Further, we demonstrate that application of CMTMR facilitates the labeling of a large number of migrating cells and enables the characterization of their phenotypes with immunohistochemical and in situ hybridization techniques. We also illustrate that CMTMR labeling is ideally suited for timelapse imaging of the behavior and dynamics of migrating cells.

Tangential Migration in Neocortical Development

Developmental Biology, 2002

During cortical development, different cell populations arise in the basal telencephalon and subsequently migrate tangentially to the neocortex. However, it is not clear whether these cortical cells are generated in the lateral ganglionic eminence (LGE), the medial ganglionic eminence (MGE), or both. In this study, we have generated a three-dimensional reconstruction to study the morphological formation of the two ganglionic eminences and the interganglionic sulcus. As a result, we have demonstrated the importance of the development of these structures for this tangential migration to the neocortex. We have also used the tracers DiI and BDA in multiple experimental paradigms (whole embryo culture, in utero injections, and brain slice cultures) to analyze the routes of cell migration and to demonstrate the roles of both eminences in the development of the cerebral cortex. These results are further strengthened, confirming the importance of the MGE in this migration and demonstrating the early generation of tangential migratory cells in the LGE early in development. Finally, we show that the calcium-binding protein Calretinin is expressed in some of these tangentially migrating cells. Moreover, we describe the spatiotemporal sequence of GABA, Calbindin, and Calretinin expression, showing that these three markers are expressed in the cortical neuroepithelium over several embryonic days, suggesting that the cells migrating tangentially form a heterogeneous population. © 2002 Elsevier Science (USA)

Neuronal migration mechanisms in development and disease

Current Opinion in Neurobiology, 2010

Neuronal migration is a fundamental process that determines the final allocation of neurons in the nervous system, establishing the basis for the subsequent wiring of neural circuitry. From cell polarization to target identification, neuronal migration integrates multiple cellular and molecular events that enable neuronal precursors to move across the brain to reach their final destination. In this review we summarize novel findings on the key processes that govern the cell biology of migrating neurons, describing recent advances in their molecular regulation in different migratory pathways of the brain, spinal cord, and peripheral nervous system. We will also review how this basic knowledge is contributing to a better understanding of the etiology and pathophysiology of multiple neurological syndromes in which neuronal migration is disrupted.

Cell-autonomous and cell-to-cell signalling events in normal and altered neuronal migration

European Journal of Neuroscience, 2011

The cerebral cortex is a complex six-layered structure that contains an important diversity of neurons, and has rich local and extrinsic connectivity. Among the mechanisms governing the cerebral cortex construction, neuronal migration is perhaps the most crucial as it ensures the timely formation of specific and selective neuronal circuits. Here, we review the main extrinsic and extrinsic factors involved in regulating neuronal migration in the cortex and describe some environmental factors interfering with their actions.

Modes and Mishaps of Neuronal Migration in the Mammalian Brain

Journal of Neuroscience, 2008

The ability of neurons to migrate to their appropriate positions in the developing brain is critical to brain architecture and function. Recent research has elucidated different modes of neuronal migration and the involvement of a host of signaling factors in orchestrating the migration, as well as vulnerabilities of this process to environmental and genetic factors. Here we discuss the role of cytoskeleton, motor proteins, and mechanisms of nuclear translocation in radial and tangential migration of neurons. We will also discuss how these and other events essential for normal migration of neurons can be disrupted by genetic and environmental factors that contribute to neurological disease in humans.