β1 Integrin Maintains Integrity of the Embryonic Neocortical Stem Cell Niche

Loulier, Karine; Lathia, Justin D.; Marthiens, Véronique; Relucio, Jenne; Mughal, Mohamed R.; Tang, Sung‐Chun; Coksaygan, Turhan; Hall, Peter; Chigurupati, Srinivasulu; Patton, Bruce L.; Colognato, Holly; Rao, Mahendra S.; Mattson, Mark P.; Haydar, Tarik F.; ffrench‐Constant, Charles

doi:10.1371/journal.pbio.1000176

Cited by 155 publications

(192 citation statements)

References 54 publications

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“…NSCs express the a6b1 integrin, and infusion of an integrin-neutralizing antibody into the lateral ventricle of adult mice released SVZ cells from the vasculature and increased cell proliferation. A similar phenotype was observed in the embryo using blocking antibodies against b1 integrin (Loulier et al 2009). The b8 integrin, which is required for the integrin-mediated activation of latent transforming growth factor-b1 (TGF-b1) and for inducing canonical TGF-b receptor signaling (Sheppard 2004), also regulates neurovascular interactions.…”

Section: The Neurovascular Niche For Neurogenesissupporting

confidence: 64%

Molecular Parallels between Neural and Vascular Development

Eichmann

Thomas

2012

Cold Spring Harbor Perspectives in Medicine

109

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The human central nervous system (CNS) features a network of 400 miles of blood vessels that receives .20% of the body's cardiac output and uses most of its blood glucose. Many human diseases, including stroke, retinopathy, and cancer, are associated with the biology of CNS blood vessels. These vessels originate from extrinsic cell populations, including endothelial cells and pericytes that colonize the CNS and interact with glia and neurons to establish the blood -brain barrier and control cerebrovascular exchanges. Neurovascular interactions also play important roles in adult neurogenic niches, which harbor a unique population of neural stem cells that are intimately associated with blood vessels. We here review the cellular and molecular mechanisms required to establish the CNS vascular network, with a special focus on neurovascular interactions and the functions of vascular endothelial growth factors.

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Section: The Neurovascular Niche For Neurogenesissupporting

confidence: 64%

Molecular Parallels between Neural and Vascular Development

Eichmann

Thomas

2012

Cold Spring Harbor Perspectives in Medicine

109

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“…NSCs are embedded in the laminin-rich ECM and also express various integrin molecules (Kazanis et al, 2010). Blocking the function of specific integrins in NSCs using neutralizing monoclonal antibodies enhances precursor proliferation and migration and promotes the depletion of NSCs from the niche (Loulier et al, 2009). The lamininintegrin-mediated interaction also contributes to the development of the NSC niche and the maintenance of its integrity (Loulier et al, 2009).…”

Section: Controlling Stem Cell Self-renewal Via Signalingmentioning

confidence: 99%

Adhesion in the stem cell niche: biological roles and regulation

2013

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Stem cell self-renewal is tightly controlled by the concerted action of stem cell-intrinsic factors and signals within the niche. Niche signals often function within a short range, allowing cells in the niche to self-renew while their daughters outside the niche differentiate. Thus, in order for stem cells to continuously self-renew, they are often anchored in the niche via adhesion molecules. In addition to niche anchoring, however, recent studies have revealed other important roles for adhesion molecules in the regulation of stem cell function, and it is clear that stem cell-niche adhesion is crucial for stem cell self-renewal and is dynamically regulated. Here, we highlight recent progress in understanding adhesion between stem cells and their niche and how this adhesion is regulated.

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“…We found that majority of cortical neurons transfected with the control vector pCAG-IRES-EGFP migrated to upper layers and exhibited normal axon projection toward Figure 8A, top row). Given that laminin/integrin signaling may act during neurogenesis to provide the stem cell niche [48], we only analyzed morphology of neurons that already reached the cortical plate at P3 and exhibited positive staining for neuronal marker Tuj1 (Supplementary information, Figure S11). We found that ablation of Itgb1 caused a marked reduction in the percentage of axon-bearing neurons, which had only short apical dendrite-like processes ( Figure 8A, bottom row), confirming the importance of Itgb1 signaling in axon formation.…”

Section: Itgb1 Is Required For Axon Formation In Cortical Neurons In mentioning

confidence: 99%

“…A recent report shows that the laminin/integrin signaling is necessary for maintaining neocortical stem cell niche and the orientation of neural stem cell division [48]. Thus, neuroepithelial cell polarity may be causally related to postmitotic neuron polarity [2], i.e., postmitotic neurons directly inherit the intrinsic apico-basal polarity of their progenitors, which are determined by laminin/ integrin signaling.…”

Section: Essential Role Of Laminin/integrin Signaling In Axon Formationmentioning

confidence: 99%

Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

et al. 2012

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Axon specification during neuronal polarization is closely associated with increased microtubule stabilization in one of the neurites of unpolarized neuron, but how this increased microtubule stability is achieved is unclear. Here, we show that extracellular matrix (ECM) component laminin promotes neuronal polarization via regulating directional microtubule assembly through β1 integrin (Itgb1). Contact with laminin coated on culture substrate or polystyrene beads was sufficient for axon specification of undifferentiated neurites in cultured hippocampal neurons and cortical slices. Active Itgb1 was found to be concentrated in laminin-contacting neurites. Axon formation was promoted and abolished by enhancing and attenuating Itgb1 signaling, respectively. Interestingly, laminin contact promoted plus-end microtubule assembly in a manner that required Itgb1. Moreover, stabilizing microtubules partially prevented polarization defects caused by Itgb1 downregulation. Finally, genetic ablation of Itgb1 in dorsal telencephalic progenitors caused deficits in axon development of cortical pyramidal neurons. Thus, laminin/Itgb1 signaling plays an instructive role in axon initiation and growth, both in vitro and in vivo, through the regulation of microtubule assembly. This study has established a linkage between an extrinsic factor and intrinsic cytoskeletal dynamics during neuronal polarization.

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β1 Integrin Maintains Integrity of the Embryonic Neocortical Stem Cell Niche

Abstract: IInteractions between laminins and integrin receptors hold neural stem cells in place at the ventricular surface of embryonic brain. Transient disruption leads to abnormal stem cell divisions and permanent cortical malformation.

Cited by 155 publications

References 54 publications

Molecular Parallels between Neural and Vascular Development

Molecular Parallels between Neural and Vascular Development

Adhesion in the stem cell niche: biological roles and regulation

Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

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