Neuronal Migration Generates New Populations of Neurons That Develop Unique Connections, Physiological Properties and Pathologies (original) (raw)

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.

Direct Evidence for Homotypic, Glia-Independent Neuronal Migration

Neuron, 1997

migration occurs in the anterior forebrain of neonatal Valencia University and adult rodents (Luskin, 1993; Lois and Alvarez-Buylla, Spain 1994). Neuronal precursors born in the subventricular zone (SVZ) of lateral ventricles migrate 3-8 mm tangentially through the SVZ (Doetsch and Alvarez-Buylla, Summary 1996) and along its anterior extension, called the rostral migratory stream (RMS), to reach the olfactory bulb Neuronal precursors born in the subventricular zone where they differentiate into granule and periglomerular (SVZ) of the neonatal and adult rodent brain migrate neurons.

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.

Neuronal migration disorders: from genetic diseases to developmental mechanisms

Trends in Neurosciences, 2000

N EURONS that leave the proliferative region in the developing telencephalon must migrate hundreds of cell-body distances to arrive at their proper position within the developing cortical plate, which gives rise to the six-layered mammalian cerebral cortex. The work of His 1 , Ramón y Cajal and others established that cortical neurons originate in the ventricular zone (VZ), migrate towards the pial surface and accumulate below the marginal zone to form the cortical plate. Rakic established that the migration of neurons traveling to the developing cortical plate is closely associated with radial-glial fibers 2. Although other work 3-5 has shown there are some neurons that do not invariably follow radial glia at all times, the central role of radial glia in organizing cortical neurons is well established. On reaching the cortex, neurons organize themselves into layers that ultimately form the adult cortex. This process of cortical lamination has been shown to be surprisingly complex. Marín-Padilla described how the earliest neurons form a precocious organization, commonly referred to as the preplate, and that the subsequent cortical plate proper deposits within this preplate 6. The deposition of newer cortical neurons divides the preplate into an outer, marginal zone (directly beneath the pial surface and basal lamina) and a deeper layer called the subplate 6. Angevine and Sidman pioneered the birthdating of neurons to establish that the neurons within the cortical plate are arranged in 'inside-out' order 7. In other words, newlyarrived cortical-plate neurons bypass the subplate, as well as the older cortical plate neurons, so that the newest neurons always add to the cortical plate directly adjacent to the marginal zone. These key observations established the foundation of cortex formation and provided a framework in which to understand mutants of cortex development (Fig. 1). Neuronal migration to the cortex lends itself to an unusually strong application of genetics, and the study of genetic disorders of cerebral cortical development in humans has played an integral role, melding itself to the study of mouse mutants. The most-familiar and certainly the best-characterized disorder of neuronal

Cell Migration in the Forebrain

Annual Review of Neuroscience, 2003

▪ The forebrain comprises an intricate set of structures that are required for some of the most complex and evolved functions of the mammalian brain. As a reflection of its complexity, cell migration in the forebrain is extremely elaborated, with widespread dispersion of cells across multiple functionally distinct areas. Two general modes of migration are distinguished in the forebrain: radial migration, which establishes the general cytoarchitectonical framework of the different forebrain subdivisions; and tangential migration, which increases the cellular complexity of forebrain circuits by allowing the dispersion of multiple neuronal types. Here, we review the cellular and molecular mechanisms underlying each of these types of migrations and discuss how emerging concepts in neuronal migration are reshaping our understanding of forebrain development in normal and pathological situations.

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.

Molecular control of neuronal migration

Bioessays, 2002

Our understanding of neuronal migration has been advanced by multidisciplinary approaches. At the cellular level, tangential and radial modes of neuronal migration contribute to different populations of neurons and have differential dependence on glial cells. At the molecular level, extracellular guidance cues have been identified and intracellular signal transduction pathways are beginning to be revealed. Interestingly, mechanisms guiding axon projection and neuronal migration appear to be conserved with those for chemotactic leukocytes. BioEssays 24:821–827, 2002. © 2002 Wiley Periodicals, Inc.

Mechanisms of neuronal migration in the adult brain

Journal of Neurochemistry, 2017

Adult neurogenesis was first observed nearly 60 years ago, and it has since grown into an important neurochemistry research field. Much recent research has focused on the treatment of brain diseases through neuronal regeneration with endogenously generated neurons. In the adult brain, immature neurons called neuroblasts are continuously generated in the ventricular-subventricular zone (V-SVZ). These neuroblasts migrate rapidly through the rostral migratory stream to the olfactory bulb, where they mature and are integrated into the neuronal circuitry. After brain insult, some of the neuroblasts in the V-SVZ migrate toward the lesion to repopulate the injured tissue. This notable migratory capacity of V-SVZ-derived neuroblasts is important for efficiently regenerating neurons in remote areas of the brain. As these neurons migrate for long distances through adult brain tissue, they are supported by various guidance cues and structures that act as scaffolds. Some of these mechanisms are unique to neuroblast migration in the adult brain, and are not involved in migration in the developing brain. Here, we review the latest findings on the mechanisms of neuroblast migration in the adult brain under physiological and pathological conditions, and discuss various issues that still need to be resolved.

New trends in neuronal migration disorders

European Journal of Paediatric Neurology, 2010

Polymicrogyria Schizencephaly a b s t r a c t Neuronal migration disorders are an heterogeneous group of disorders of nervous system development and they are considered to be one of the most significant causes of neurological and developmental disabilities and epileptic seizures in childhood. In the last ten years, molecular biologic and genetic investigations have widely increased our knowledge about the regulation of neuronal migration during development.