Semaphorin-3A guides radial migration of cortical neurons during development

Chen, Gang; Sima, Jian; Jin, Ming; Wang, Kaiyu; Xue, Xiao-jing; Wang, Zheng; Ding, Yu; Yuan, Xiao-bing

doi:10.1038/nn2018

Cited by 219 publications

(241 citation statements)

References 51 publications

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“…Although Sema3A is mainly known as an axonal repellent, it has also been shown to act as an attractant for developing dendrites and radial migration of cortical neurons (Polleux et al, 2000;Chen et al, 2008). During cortical neuron migration, Sema3A is regionally expressed and attractive for neuropilin-1-expressing neurons.…”

Section: Discussionmentioning

confidence: 99%

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

et al. 2009

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Glioblastoma multiforme (GBM) is the most malignant glioma type with diffuse borders due to extensive tumor cell infiltration. Therefore, understanding the mechanism of GBM cell dispersal is critical for developing effective therapies to limit infiltration. We identified neuropilin-1 as a mediator of cancer cell invasion by a functional proteomic screen and showed its role in GBM cells. Neuropilin-1 is a receptor for semaphorin3A (Sema3A), a secreted chemorepellent that facilitates axon guidance during neural development. Although neuropilin-1 expression in GBMs was previously shown, its role as a Sema3A receptor remained elusive. Using fluorophore-assisted light inactivation and RNA interference , we showed that neuropilin-1 is required for GBM cell migration. We also showed that GBM cells secrete Sema3A endogenously, and RNA interferencemediated downregulation of Sema3A inhibits migration and alters cell morphology that is dependent on Rac1 activity. Sema3A depletion also reduces dispersal, which is recovered by supplying Sema3A exogenously. Extracellular application of Sema3A decreases cell-substrate adhesion in a neuropilin-1-dependent manner. Using immunohistochemistry, we showed that Sema3A is overexpressed in a subset of human GBMs compared with the non-neoplastic brain. Together, these findings implicate Sema3A as an autocrine signal for neuropilin-1 to promote GBM dispersal by modulating substrate adhesion and suggest that targeting Sema3A-neuropilin-1 signaling may limit GBM infiltration.

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Section: Discussionmentioning

confidence: 99%

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

et al. 2009

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“…1). These authors went on to show that the class 3 secreted semaphorin, Sema3A, which is enriched in the most superficial part of the cortical wall (the top of the cortical plate) (see also Chen et al 2008), plays a role in repulsing axon initiation ventrally toward the ventricle (Polleux et al 1998). This work suggests that the polarized emergence of a single axon is controlled at least in part by extracellular cues expressed in a graded manner along the neuron's migratory path.…”

Section: Laminin Bdnf Sema3a and Other Cues In Mammalian Neuronsmentioning

confidence: 99%

Initiating and Growing an Axon

Polleux¹,

Snider²

2010

Cold Spring Harbor Perspectives in Biology

154

124

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The ability of neurons to form a single axon and multiple dendrites underlies the directional flow of information transfer in the central nervous system. Dendrites and axons are molecularly and functionally distinct domains. Dendrites integrate synaptic inputs, triggering the generation of action potentials at the level of the soma. Action potentials then propagate along the axon, which makes presynaptic contacts onto target cells. This article reviews what is known about the cellular and molecular mechanisms underlying the ability of neurons to initiate and extend a single axon during development. Remarkably, neurons can polarize to form a single axon, multiple dendrites, and later establish functional synaptic contacts in reductionist in vitro conditions. This approach became, and remains, the dominant model to study axon initiation and growth and has yielded the identification of many molecules that regulate axon formation in vitro (Dotti et al. 1988). At present, only a few of the genes identified using in vitro approaches have been shown to be required for axon initiation and outgrowth in vivo. In vitro, axon initiation and elongation are largely intrinsic properties of neurons that are established in the absence of relevant extracellular cues. However, the importance of extracellular cues to axon initiation and outgrowth in vivo is emerging as a major theme in neural development (Barnes and Polleux 2009). In this article, we focus our attention on the extracellular cues and signaling pathways required in vivo for axon initiation and axon extension.

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“…Interestingly, a Sema3A gradient in the developing cortex is required to maintain radial migration of embryonic cortical neurons [18] and to attract their apical dendrites toward the pial surface [19]. However, Sema3A knock-out mice show no obvious cortical lamination defects, suggesting the involvement of compensatory factors.…”

Section: L1 and Chl1 As Signaling Co-receptors In Cortical Developmentmentioning

confidence: 99%

“…* of special interest: references 3,6,18,20,26,33,37 ** of exceptional interest as follows: ** 10. The authors used BAC transgenic reporter mice expressing green fluorescent protein in an interneuron subpopulation to show that a subcellular gradient of the Neurofascin 186 isoform along the dendritic-somal-axon initial segment axis of cerebellar Purkinje cells is formed by direct interaction with an ankyrin B isoform, and is responsible for axon targeting of basket interneurons to the axon initial segment.…”

Section: Annotationsmentioning

confidence: 99%

L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth

Schmid

Maness

2008

Current Opinion in Neurobiology

191

165

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Summary of Recent AdvancesNeural cell adhesion molecules (CAMs) of the immunoglobulin superfamily engage in multiple neuronal interactions that influence cell migration, axonal and dendritic projection, and synaptic targeting. Their downstream signal transduction events specify whether a cell moves or projects axons and dendrites to targets in the brain. Many of the diverse functions of CAMs are brought about through homophilic and heterophilic interactions with other cell surface receptors. An emerging concept is that CAMs act as co-receptors to assist in intracellular signal transduction, and to provide cytoskeletal linkage necessary for cell and growth cone motility. Here we will focus on new discoveries that have revealed novel co-receptor functions for the best understood CAMs -L1, CHL1, and NCAM-important for neuronal migration and axon guidance. We will also discuss how dysregulation of CAMs may also bear on neuropsychiatric disease and cancer.

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Semaphorin-3A guides radial migration of cortical neurons during development

Cited by 219 publications

References 51 publications

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

Initiating and Growing an Axon

L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth

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