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1.
神经元迁移的细胞和分子机制   总被引:1,自引:0,他引:1  
在脑的发育过程中,神经元的正确迁移是正常脑组织发生的一个必不可少的环节。在过去的几十年中,通过不同的学科方法,对于神经元迁移的机制有了较好的理解。在细胞水平上,神经元迁移需要3个重复事件的精确调控;在分子水平,与神经元迁移相关的胞外信号分子已经被鉴定,而且大量的胞内信号通路也已经被阐明。  相似文献   

2.
Trekking across the brain: the journey of neuronal migration   总被引:12,自引:0,他引:12  
Ayala R  Shu T  Tsai LH 《Cell》2007,128(1):29-43
The correct positioning of neurons during development--achieved through directed migration--is the basis for proper brain function. Several decades of research have yielded a comprehensive map illustrating the temporal and spatial events underlying neurogenesis and neuronal migration during development. The discovery of distinct migration modes and pathways has been accompanied by the identification of a large interwoven molecular network that transmits extracellular signals into the cell. Moreover, recent work has shed new light on how the cytoskeleton is regulated and coordinated at the molecular and cellular level to execute neuronal migration.  相似文献   

3.
Sun Y  Huang Z  Yang K  Liu W  Xie Y  Yuan B  Zhang W  Jiang X 《PloS one》2011,6(11):e28156

Background

Neurons are dynamically coupled with each other through neurite-mediated adhesion during development. Understanding the collective behavior of neurons in circuits is important for understanding neural development. While a number of genetic and activity-dependent factors regulating neuronal migration have been discovered on single cell level, systematic study of collective neuronal migration has been lacking. Various biological systems are shown to be self-organized, and it is not known if neural circuit assembly is self-organized. Besides, many of the molecular factors take effect through spatial patterns, and coupled biological systems exhibit emergent property in response to geometric constraints. How geometric constraints of the patterns regulate neuronal migration and circuit assembly of neurons within the patterns remains unexplored.

Methodology/Principal Findings

We established a two-dimensional model for studying collective neuronal migration of a circuit, with hippocampal neurons from embryonic rats on Matrigel-coated self-assembled monolayers (SAMs). When the neural circuit is subject to geometric constraints of a critical scale, we found that the collective behavior of neuronal migration is spatiotemporally coordinated. Neuronal somata that are evenly distributed upon adhesion tend to aggregate at the geometric center of the circuit, forming mono-clusters. Clustering formation is geometry-dependent, within a critical scale from 200 µm to approximately 500 µm. Finally, somata clustering is neuron-type specific, and glutamatergic and GABAergic neurons tend to aggregate homo-philically.

Conclusions/Significance

We demonstrate self-organization of neural circuits in response to geometric constraints through spatiotemporally coordinated neuronal migration, possibly via mechanical coupling. We found that such collective neuronal migration leads to somata clustering, and mono-cluster appears when the geometric constraints fall within a critical scale. The discovery of geometry-dependent collective neuronal migration and the formation of somata clustering in vitro shed light on neural development in vivo.  相似文献   

4.
Immunocytochemical and histochemical methods have been used to describe the neuronal population migrating from the rat olfactory placode and to analyze the spatio-temporal evolution of this neuronal migration during development. Several neuronal markers, such as binding to the lectin Ulex europaeus (UEA I) and the presence of neuron-specific enolase (NSE), olfactory marker protein (OMP), and luteinizing hormone-releasing hormone (LHRH), have been tested in order to determine whether migrating neurons originate from both the medial and the lateral parts of the placode and whether they all express LHRH. Our data show that a large population of differentiated migrating neurons can be identified with an antibody against NSE from the 14th day of gestation and with UEA I one day later. Migrating neurons are closely associated with both the vomeronasal axon fascicles emerging from the medial pit and the olfactory axons originating from the lateral pit. However, the neuron migration from the lateral pit appears to be more discrete than that from the medial pit. No LHRH immunoreactivity has been detected among neurons migrating from the lateral pit. Some neurons accompanying the olfactory axon fascicles exhibit a high level of maturation as shown by their OMP-positivity. Numerous neurons positive for both NSE and UEA I have also been observed within the presumptive olfactory nerve layer in early embryonic stages.  相似文献   

5.
Extracellular matrix (ECM) glycoproteins are expressed in the central nervous system (CNS) in complex and developmentally regulated patterns. The ECM provides a number of critical functions in the CNS, contributing both to the overall structural organization of the CNS and to control of individual cells. At the cellular level, the ECM affects its functions by a wide range of mechanisms, including providing structural support to cells, regulating the activity of second messenger systems, and controlling the distribution and local concentration of growth and differentiation factors. Perhaps the most well known role of the ECM is as a substrate on which motile cells can migrate. Genetic, cell biological, and biochemical studies provide strong evidence that ECM glycoproteins such as laminins, tenascins, and proteoglycans control neuronal migration and positioning in several regions of the developing and adult brain. Recent findings have also shed important new insights into the cellular and molecular mechanisms by which reelin regulates migration. Here we will summarize these findings, emphasizing the emerging concept that ECM glycoproteins promote different modes of neuronal migration such as radial, tangential, and chain migration. We also discuss several studies demonstrating that mutations in ECM glycoproteins can alter neuronal positioning by cell nonautonomous mechanisms that secondarily affect migrating neurons.  相似文献   

6.
A new gene from the distal short arm of the human X chromosome has recently been cloned and characterized. Mutations in this gene lead to the neuronal migration defect observed in Kallmann syndrome. Although there is no direct proof for the involvement of this gene in neuronal migration, significant similarities between its predicted protein product and neural adhesion molecules have been found. X-linked Kallmann syndrome represents the first example in vertebrates of a neuronal migration defect for which the gene has been isolated.  相似文献   

7.
Proper migration of neuronal somas and axonal growth cones to designated locations in the developing brain is essential for the assembly of functional neuronal circuits.Rapid progress in research of axon guidance and neuronal migration has been made in the last twenty years.Chinese researchers began their exploration in this field ten years ago and have made significant contributions in clarifying the signal transduction of axon guidance and neuronal migration.Several unique experimental approaches,includin...  相似文献   

8.
Following terminal mitosis, neuronal precursor cells leave their site of origin and migrate towards their definitive site of residency. In order to establish the intricate cytoarchitecture described in the adult human brain, neuronal migration must be finely regulated. In humans, brain malformations can result from neuronal migration defects. The spectrum of migration disorder severity extends from few heterotopic neurons, as observed in periventricular heterotopia, to a complete cortical disorganization, as observed in cases of lissencephaly. Recently, specific migration disorders have been linked to mutations/deletions in the doublecortin, filamin-1, LIS1 and reelin genes. These proteins act at different levels of the signaling cascades transducing extracellular guiding cues into cytoskeletal reorganization. Here, we summarize the data concerning these four molecules and speculate on their functions and interaction partners during neuronal development.  相似文献   

9.
10.
Cell-cell interactions play a key role in tissue homeostasis. Intercellular adhesions share the complex task of establishing and maintaining tissue architecture while allowing tissue growth, renewal and repair. In particular, adherens junctions (AJs) have been implicated in the formation of diverse tissues and organs like epitheliums, blood vessels or the central nervous system. At the cellular level, AJs are well known for their essential role in epithelial cell differentiation and baso-apical polarity. They also contribute to the control of cell polarity to promote neuronal morphogenesis, growth cone guidance and directed migration in a variety of cell types during embryonic development. AJs based on classical cadherin- and nectin-mediated cell-cell interactions control local membrane dynamics to polarize cell morphology and motility at the single cell level and to coordinate cell shape changes and motile behaviour at the tissue level. I review here the molecular mechanisms allowing control of polarized cell morphology and motility by AJs.  相似文献   

11.
p27(kip1), a cyclin-dependent kinase (CDK) inhibitor (CKI), generally suppresses CDK activity in proliferating cells. Although another role of p27 in cell migration has been recently suggested in vitro, the physiological importance of p27 in cell migration remains elusive, as p27-deficient mice have not shown any obvious migration-defect-related phenotypes. Here, we show that Cdk5, an unconventional neuronal CDK, phosphorylates and stabilizes p27 as an upstream regulator, maintaining the amount of p27 in post-mitotic neurons. In vivo RNA interference (RNAi) experiments showed that reduced amounts of p27 caused inhibition of cortical neuronal migration and decreased the amount of F-actin in the processes of migrating neurons. The Cdk5-p27 pathway activates an actin-binding protein, cofilin, which is also shown to be involved in cortical neuronal migration in vivo. Our findings shed light on a previously unknown new relationship between CDK and CKI in G0-arrested cells that regulates cytoskeletal reorganization and neuronal migration during corticogenesis.  相似文献   

12.
During a study of the genetics of nuclear migration in the filamentous fungus Aspergillus nidulans, we cloned a gene, nudF, which is required for nuclear migration during vegetative growth as well as development. The NUDF protein level is controlled by another protein NUDC, and extra copies of the nudF gene can suppress the nudC3 mutation. nudF encodes a protein with 42% sequence identity to the human LIS-1 (Miller-Dieker lissencephaly-1) gene, which is required for proper neuronal migration during brain development. This strong similarity suggests that the LIS-1 gene product may have a function similar to that of NUDF and supports previous findings to suggest that nuclear migration may play a role in neuronal migration.  相似文献   

13.
Neuronal precursors remain in the proliferative zone of the developing mammalian neocortex until after they have undergone neuronal differentiation and cell cycle arrest. The newborn neurons then migrate away from the proliferative zone and enter the cortical plate. The molecules that coordinate migration with neuronal differentiation have been unclear. We have proposed in this study that the cdk inhibitors p57 and p27 play a role in this coordination. We have found that p57 and p27 mRNA increase upon neuronal differentiation of neocortical neuroepithelial cells. Knockdown of p57 by RNA interference resulted in a significant delay in the migration of neurons that entered the cortical plate but did not affect neuronal differentiation. Knockdown of p27 also inhibits neuronal migration in the intermediate zone as well as in the cortical plate, as reported by others. We have also found that knockdown of p27 increases p57 mRNA levels. These results suggest that both p57 and p27 play essential roles in neuronal migration and may, in concert, coordinate the timing of neuronal differentiation, migration, and possibly cell cycle arrest in neocortical development.  相似文献   

14.
Antisera to calmodulin, a Ca2%-dependent modulator protein, and a heat- labile calmodulin-binding protein have been used to localize these proteins in mouse caudate-putamen. The two proteins appear to be located at identical sites in this brain area. At the light microscopic level, calmodulin and calmodulin-binding protein are found within the cytoplasm and processes of large cells. At the electron microscopic level the proteins are associated with neuronal elements only, primarily at postsynaptic sites within neuronal somata and dendrites. Within the dendrites the immunocytochemical label is associated predominantly with the postsynaptic density and dendritic microtubules. These results are in accord with recent biochemical and immunihistochemical studies of calmodulin in brain and in dividing cells. Thus, calmodulin and the heat-labile calmodulin-binding protein may play a role in the nervous system at the site of neurotransmitter action and at the level of microtubular function.  相似文献   

15.
16.
The centrosome is crucial for neuronal migration and polarisation, processes that are disrupted in a number of neurodevelopmental disorders including schizophrenia. Mutation of DISC1, associated with increased risk of schizophrenia and psychiatric illness, has been shown to affect the centrosome, but the mechanisms involved have not been elucidated. In this issue of EMBO Reports, Fukuda and colleagues demonstrate that a DISC1‐interacting protein, CAMDI, suppresses the activity of the histone deacetylase HDAC6, thereby promoting centrosome stability and consequently neuronal migration 1 . Loss of CAMDI leads to cortical migration defects and behavioural phenotypes that model autism spectrum disorders and which can be rescued by inhibition of HDAC6. The study provides novel mechanistic insight into centrosome regulation in neurodevelopment.  相似文献   

17.
During development, neurons migrate to the cortex radially from periventricular germinative zones as well as tangentially from ganglionic eminences. The vast majority of cortical neurons settle radially in the cortical plate. Neuronal migration requires an exquisite regulation of leading edge extension, nuclear translocation (nucleokinesis), and retraction of trailing processes. During the past few years, several genes and proteins have been identified that are implicated in neuronal migration. Many have been characterized by reference to known mechanisms of neuronal and non-neuronal cell migration in culture; however, probably the most interesting have been identified by gene inactivation or modification in mice and by positional cloning of brain malformation genes in humans and mice. Although it is impossible to provide a fully integrated view, some patterns clearly emerge and are the subject of this article. Specific emphasis is placed on three aspects: first, the role of the actin treadmill, with cyclic formation of filopodial and lamellipodial extensions, in relation to surface events that occur at the leading edge of radially migrating neurons; second, the regulation of microtubule dynamics, which seems to play a key role in nucleokinesis; and third, the mechanisms by which the extracellular protein Reelin regulates neuronal positioning at the end of migration.  相似文献   

18.
神经元的迁移机制   总被引:3,自引:0,他引:3  
在脊椎动物的脑发育过程中,未成熟的神经元在时间和空间上的精确迁移到达最后行使功能的目的地,是中枢神经系统发育的一个重要阶段.最近的研究结果表明这一过程涉及到一系列分子事件,包括细胞表面分子的相互作用、离子通道的激活和细胞骨架的作用等.对这些事件的了解不但有助于了解神经元迁移的机制,而且对阐明由于神经元异常迁移而引起的脑紊乱失调等病理现象的机理都是必要的.  相似文献   

19.
Establishment of axon and dendrite polarity, migration to a desired location in the developing brain, and establishment of proper synaptic connections are essential processes during neuronal development. The cellular and molecular mechanisms that govern these processes are under intensive investigation. The function of the centrosome in neuronal development has been examined and discussed in few recent studies that underscore the fundamental role of the centrosome in brain development. Clusters of emerging studies have shown that centrosome positioning tightly regulates neuronal development, leading to the segregation of cell factors, directed neurite differentiation, neuronal migration, and synaptic integration. Furthermore, cilia, that arise from the axoneme, a modified centriole, are emerging as new regulatory modules in neuronal development in conjunction with the centrosome. In this review, we focus on summarizing and discussing recent studies on centrosome positioning during neuronal development and also highlight recent findings on the role of cilia in brain development. We further discuss shared molecular signaling pathways that might regulate both centrosome and cilia associated signaling in neuronal development. Furthermore, molecular determinants such as DISC1 and LKB1 have been recently demonstrated to be crucial regulators of various aspects of neuronal development. Strikingly, these determinants might exert their function, at least in part, via the regulation of centrosome and cilia associated signaling and serve as a link between these two signaling centers. We thus include an overview of these molecular determinants.  相似文献   

20.
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