Polarized Increase of Calcium and Nucleokinesis in Tangentially Migrating Neurons (original) (raw)
Related papers
2004
Cortical interneurons originate from the ganglionic eminences and reach their final position in the cortex via tangential migratory routes. The mechanisms of this migration are poorly understood. Here we have performed confocal time-lapse analysis of cell movement in the intermediate zone of embryonic mouse cortical slices in order to directly visualize their mode of migration. Tangentially migrating neurons moved by nucleokinesis, characterized by active phases of discontinuous advances of the nucleus followed by periods of quies-cence. Dissociated cells from the ganglionic eminences also showed nucleokinesis associated with an increase of intracellular calcium, [Ca2+]i Calcium elevation was greatest in the proximal region of the leading process, a zone with a wide distribution of γ-tubulin. General increases in [Ca2+]i elicited by microperfussion with neurotrans-mitters did not elicit nucleokinesis. These results show that tangen-tial migration uses nucleokinesis, a cell-intrinsic...
Receptor-activated calcium signals in tangentially migrating cortical cells
Cerebral Cortex
Recent studies have shown that the two main types of cortical neurons, pyramidal and nonpyramidal, have different origins and use different migratory routes--radial and tangential respectively. The role of neurotransmitters in radial migration is well known; however, there are no data about their effect on intracellular calcium--[Ca(2+)](i)--in tangentially migrating cells. We have performed ratiometric and confocal calcium imaging of 1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine labelled tangentially migrating neurons in the intermediate zone cells of fetal rat coronal slices. Superfusion with N-methyl-D-aspartic acid (NMDA) leads to an increase in [Ca(2+)](i), which is blocked by the antagonist APV or the presence of Mg(2+) in the medium. Kainate produced an increase in [Ca(2+)](i) that could be blocked by the non-NMDA antagonist CNQX. Muscimol, an agonist of GABAa-receptors, produced a transitory increase in [Ca(2+)](i) that was blocked by the specific antago...
F1000 - Post-publication peer review of the biomedical literature, 2005
During rodent cortex development, cells born in the medial ganglionic eminence (MGE) of the basal telencephalon reach the embryonic cortex by tangential migration and differentiate as interneurons. Migrating MGE cells exhibit a saltatory progression of the nucleus and continuously extend and retract branches in their neuritic arbor. We have analyzed the migration cycle of these neurons using in vitro models. We show that the nucleokinesis in MGE cells comprises two phases. First, cytoplasmic organelles migrate forward, and second, the nucleus translocates toward these organelles. During the first phase, a large swelling that contains the centrosome and the Golgi apparatus separates from the perinuclear compartment and moves rostrally into the leading neurite, up to 30 m from the waiting nucleus. This long-distance migration is associated with a splitting of the centrioles that line up along a linear Golgi apparatus. It is followed by the second, dynamic phase of nuclear translocation toward the displaced centrosome and Golgi apparatus. The forward movement of the nucleus is blocked by blebbistatin, a specific inhibitor of nonmuscle myosin II. Because myosin II accumulates at the rear of migrating MGE cells, actomyosin contraction likely plays a prominent role to drive forward translocations of the nucleus toward the centrosome. During this phase of nuclear translocation, the leading growth cone either stops migrating or divides, showing a tight correlation between leading edge movements and nuclear movements.
Journal of Neuroscience, 2010
Neuronal migration is a complex process requiring the coordinated interaction of cytoskeletal components and regulated by calcium signaling among other factors. Migratory neurons are polarized cells in which the largest intracellular organelle, the nucleus, has to move repeatedly. Current views support a central role for pulling forces that drive nuclear movement. The participation of actomyosin driven forces acting at the nucleus rear has been suggested, however its precise contribution has not been directly addressed. By analyzing interneurons migrating in cortical slices of mouse brains, we have found that nucleokinesis is associated with a precise pattern of actin dynamics characterized by the initial formation of a cup-like actin structure at the rear nuclear pole. Time-lapse experiments show that progressive actomyosin contraction drives the nucleus forward. Nucleokinesis concludes with the complete contraction of the cup-like structure, resulting in an actin spot at the base of the retracting trailing process. Our results demonstrate that this actin remodeling requires a threshold calcium level provided by low-frequency spontaneous fast intracellular calcium transients. Microtubule stabilization with taxol treatment prevents actin remodeling and nucleokinesis, whereas cells with a collapsed microtubule cytoskeleton induced by nocodazole treatment, display nearly normal actin dynamics and nucleokinesis. In summary, the results presented here demonstrate that actomyosin forces acting at the rear side of the nucleus drives nucleokinesis in tangentially migrating interneurons in a process that requires calcium and a dynamic cytoskeleton of microtubules.
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)
Guiding neuronal cell migrations
Cold Spring Harbor perspectives in biology, 2010
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 circuitries. 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.
Brain Sciences, 2017
Neuronal migration is a fundamental biological process that underlies proper brain development and neuronal circuit formation. In the developing cerebral cortex, distinct neuronal populations, producing excitatory, inhibitory and modulatory neurotransmitters, are generated in different germinative areas and migrate along various routes to reach their final positions within the cortex. Different technical approaches and experimental models have been adopted to study the mechanisms regulating neuronal migration in the cortex. In this review, we will discuss the most common in vitro, ex vivo and in vivo techniques to visualize and study cortical neuronal migration.
Dynamics of Cell Migration from the Lateral Ganglionic Eminence in the Rat
The Journal of Neuroscience, 1996
From previous developmental studies, it has been proposed that the neurons of the ventrolateral cortex, including the primary olfactory cortex, differentiate from progenitor cells in the lateral ganglionic eminence. The objective of the present study was to test this hypothesis. The cells first generated in the forebrain of the rat migrate to the surface of the telencephalic vesicle by embryonic day (E) 12. Using [ 3 H]thymidine, we found that most of these cells contributed to the formation of the deep layer III of the primary olfactory cortex. To study the migratory routes of these cells, we made localized injections of the carbocyanine fluorescent tracers DiI and DiA into various parts of the lateral ganglionic eminence in living embryos at E12-E14 and subsequently maintained the embryos in a culture device for 17-48 hr. After fixation, most migrating cells were located at the surface of the telencephalic vesicle, whereas others were seen coursing tangentially into the preplate. Injections made at E13 and in fixed tissue at E15 showed that migrating cells follow radial glial fibers extending from the ventricular zone of the lateral ganglionic eminence to the ventrolateral surface of the telencephalic vesicle. The spatial distribution of radial glial fibers was studied in Golgi preparations, and these observations provided further evidence of the existence of long glial fibers extending from the ventricular zone of the lateral ganglionic eminence to the ventrolateral cortex. We conclude that cells of the primary olfactory cortex derive from the lateral ganglionic eminence and that some early generated cells migrating from the lateral ganglionic eminence transgress the cortico-striatal boundary entering the preplate of the neocortical primordium.
Migration of Neocortical Neurons in the Absence of Functional NMDA Receptors
Molecular and Cellular Neuroscience, 1997
A variety of factors, from cell adhesion to changes in intracellular calcium, are thought to influence neuronal migration. Here we examine the possibility that calcium influx mediated via NMDA receptors regulates migration of neocortical neurons. We have examined the cytoarchitecture of the cortex in transgenic mice lacking functional NMDA receptors. Using cell birthdating techniques we found that cells in the developing neocortex of NMDAR-1 mutant mice have a distribution indistinguishable from that in animals with functional NMDA receptors, implying normal rates and routes of migration. These observations contrast with previous in vitro pharmacological studies of cerebellar granule cell migration, in which a role for NMDA receptors has been demonstrated. Thus, either different mechanisms are responsible for controlling neuronal migration in neocortex versus cerebellum or, more likely, neocortical neurons in NMDAR-1 mutant mice have acquired compensatory mechanisms for cell migration.