Diverse functions of perlecan in central nervous system cells <i>in vitro</i>

Nakamura, Ryosuke; Nakamura, Fumio; Fukunaga, Shigeharu

doi:10.1111/asj.12376

Cited by 14 publications

(8 citation statements)

References 28 publications

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“…Additionally, perlecan surrounds axonal fascicle bundles from olfactory sensory neurons in embryonic mice (Shay et al, 2008 ). Perlecan can also promote neurite extension in vitro (Nakamura et al, 2015 ). In chick embryos, the expression pattern of this protein has been studied until HH17, where, as in the present report, perlecan becomes circumscribed to the external limiting membrane (Soulintzi and Zagris, 2007 ) and does not appear to participate in axon guidance.…”

Section: Discussionmentioning

confidence: 99%

Expression Patterns of Extracellular Matrix Proteins during Posterior Commissure Development

et al. 2016

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Extracellular matrix (ECM) molecules are pivotal for central nervous system (CNS) development, facilitating cell migration, axonal growth, myelination, dendritic spine formation, and synaptic plasticity, among other processes. During axon guidance, the ECM not only acts as a permissive or non-permissive substrate for navigating axons, but also modulates the effects of classical guidance cues, such as netrin or Eph/ephrin family members. Despite being highly important, little is known about the expression of ECM molecules during CNS development. Therefore, this study assessed the molecular expression patterns of tenascin, HNK-1, laminin, fibronectin, perlecan, decorin, and osteopontin along chick embryo prosomere 1 during posterior commissure development. The posterior commissure is the first transversal axonal tract of the embryonic vertebrate brain. Located in the dorso-caudal portion of prosomere 1, posterior commissure axons primarily arise from the neurons of basal pretectal nuclei that run dorsally to the roof plate midline, where some turn toward the ipsilateral side. Expressional analysis of ECM molecules in this area these revealed to be highly arranged, and molecule interactions with axon fascicles suggested involvement in processes other than structural support. In particular, tenascin and the HNK-1 epitope extended in ventro-dorsal columns and enclosed axons during navigation to the roof plate. Laminin and osteopontin were expressed in the midline, very close to axons that at this point must decide between extending to the contralateral side or turning to the ipsilateral side. Finally, fibronectin, decorin, and perlecan appeared unrelated to axonal pathfinding in this region and were instead restricted to the external limiting membrane. In summary, the present report provides evidence for an intricate expression of different extracellular molecules that may cooperate in guiding posterior commissure axons.

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Section: Discussionmentioning

confidence: 99%

Expression Patterns of Extracellular Matrix Proteins during Posterior Commissure Development

et al. 2016

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“…Behavioral testing took place prior to (baseline) MCAo surgery and on PSD 1,4,6,8,11,13,15,18, and 20. Mice were placed on the rotor-rod (San Diego Instruments) for 5 min with increasing acceleration (0-40 rpm, 3 trials) measuring total distance (cm).…”

Section: Behavioral Testingmentioning

confidence: 99%

“…Importantly, complete perlecan knockout is embryonic lethal, and mice have brain atrophy associated with reduced cell proliferation, hampered migration of developing neurons, and impaired neurogenesis [13,14]. Conversely, perlecan treatment promotes in vitro neural stem/progenitor cell proliferation and neuritogenesis [15]. Collectively, this suggests a key role of perlecan in developmental neurogenesis.…”

Section: Introductionmentioning

confidence: 99%

Perlecan Domain-V Enhances Neurogenic Brain Repair After Stroke in Mice

Trout

Kahle

Roberts

et al. 2020

Transl. Stroke Res.

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The extracellular matrix fragment perlecan domain V is neuroprotective and functionally restorative following experimental stroke. As neurogenesis is an important component of chronic post-stroke repair, and previous studies have implicated perlecan in developmental neurogenesis, we hypothesized that domain V could have a broad therapeutic window by enhancing neurogenesis after stroke. We demonstrated that domain V is chronically increased in the brains of human stroke patients, suggesting that it is present during post-stroke neurogenic periods. Furthermore, perlecan deficient mice had significantly less neuroblast precursor cells after experimental stroke. Seven-day delayed domain V administration enhanced neurogenesis and restored peri-infarct excitatory synaptic drive to neocortical layer 2/3 pyramidal neurons after experimental stroke. Domain V's effects were inhibited by blockade of α2β1 integrin, suggesting the importance of α2β1 integrin to neurogenesis and domain V neurogenic effects. Our results demonstrate that perlecan plays a previously unrecognized role in post-stroke neurogenesis and that delayed DV administration after experimental stroke enhances neurogenesis and improves recovery in an α2β1 integrin-mediated fashion. We conclude that domain V is a clinically relevant neuroprotective and neuroreparative novel stroke therapy with a broad therapeutic window.

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“…In vitro studies by Nakamura et al ( 2015 ) demonstrated addition of exogenous perlecan to neural cultures promoted NSPC proliferation as well as neurite extension. Addition of heparin was found to promote NSPC proliferation, although this was not significant, suggesting perlecan as well as its associated GAGs are required.…”

Section: Hspgs and Neurogenesismentioning

confidence: 99%

Exploiting Heparan Sulfate Proteoglycans in Human Neurogenesis—Controlling Lineage Specification and Fate

Griffiths

Haupt

2017

Front. Integr. Neurosci.

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Unspecialized, self-renewing stem cells have extraordinary application to regenerative medicine due to their multilineage differentiation potential. Stem cell therapies through replenishing damaged or lost cells in the injured area is an attractive treatment of brain trauma and neurodegenerative neurological disorders. Several stem cell types have neurogenic potential including neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs). Currently, effective use of these cells is limited by our lack of understanding and ability to direct lineage commitment and differentiation of neural lineages. Heparan sulfate proteoglycans (HSPGs) are ubiquitous proteins within the stem cell microenvironment or niche and are found localized on the cell surface and in the extracellular matrix (ECM), where they interact with numerous signaling molecules. The glycosaminoglycan (GAG) chains carried by HSPGs are heterogeneous carbohydrates comprised of repeating disaccharides with specific sulfation patterns that govern ligand interactions to numerous factors including the fibroblast growth factors (FGFs) and wingless-type MMTV integration site family (Wnts). As such, HSPGs are plausible targets for guiding and controlling neural stem cell lineage fate. In this review, we provide an overview of HSPG family members syndecans and glypicans, and perlecan and their role in neurogenesis. We summarize the structural changes and subsequent functional implications of heparan sulfate as cells undergo neural lineage differentiation as well as outline the role of HSPG core protein expression throughout mammalian neural development and their function as cell receptors and co-receptors. Finally, we highlight suitable biomimetic approaches for exploiting the role of HSPGs in mammalian neurogenesis to control and tailor cell differentiation into specific lineages. An improved ability to control stem cell specific neural lineage fate and produce abundant cells of lineage specificity will further advance stem cell therapy for the development of improved repair of neurological disorders. We propose a deeper understanding of HSPG-mediated neurogenesis can potentially provide novel therapeutic targets of neurogenesis.

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Diverse functions of perlecan in central nervous system cells in vitro

Cited by 14 publications

References 28 publications

Expression Patterns of Extracellular Matrix Proteins during Posterior Commissure Development

Expression Patterns of Extracellular Matrix Proteins during Posterior Commissure Development

Perlecan Domain-V Enhances Neurogenic Brain Repair After Stroke in Mice

Exploiting Heparan Sulfate Proteoglycans in Human Neurogenesis—Controlling Lineage Specification and Fate

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