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

Lei, Wenliang; Xing, Shige; Deng, Cai-Yun; Ju, Xiang-Chun; Jiang, Xingyu; Luo, Zhen-Ge

doi:10.1038/cr.2012.40

Cited by 64 publications

(46 citation statements)

References 74 publications

(116 reference statements)

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“…MetaCore data analysis [Fig. (D)] shows that miR‐29c putatively targets ITGB1 that is known to regulate axonal function (Lei et al, ). A series of experiments were conducted to assay the cause‐effect of axonal miR‐29c on axonal growth.…”

Section: Resultsmentioning

confidence: 99%

MicroRNAs in the axon locally mediate the effects of chondroitin sulfate proteoglycans and cGMP on axonal growth

Zhang

Chopp

Liu

et al. 2015

Developmental Neurobiology

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Axonal miRNAs locally regulate axonal growth by modulating local protein composition. Whether localized miRNAs in the axon mediate the inhibitory effect of CSPGs on the axon remains unknown. We showed that in cultured cortical neurons, axonal application of CSPGs inhibited axonal growth and altered axonal miRNA profiles, whereas elevation of axonal cGMP levels by axonal application of sildenafil reversed the effect of CSPGs on inhibition of axonal growth and on miRNA profiles. Specifically, CSPGs elevated and reduced axonal levels of miR-29c and ITGB1 proteins, respectively, while elevation of cGMP levels overcame these CSPG effects. Gain-of- and loss-of-function experiments demonstrated that miR-29c in the distal axon mediates axonal growth downstream of CSPGs and cGMP by regulating axonal protein levels of ITGB1, FAK, and RhoA. Together, our data demonstrate that axonal miRNAs play an import role in mediating the inhibitory action of CSPGs on axonal growth and that miR-29c at least partially mediates this process.

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Section: Resultsmentioning

confidence: 99%

MicroRNAs in the axon locally mediate the effects of chondroitin sulfate proteoglycans and cGMP on axonal growth

Zhang

Chopp

Liu

et al. 2015

Developmental Neurobiology

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“…Whether neurite initiation and migration in vivo are inextricably linked or autonomous processes thus remains unclear. Interestingly, neurons can migrate without axon extension, 17,20 indicating that at least polarization and migration can be independently regulated. If care is taken to not over interpret the findings, it should be useful to apply the basic principles learned from neuronal culture studies to the in vivo setting.…”

Section: Downloaded By [Mcmaster University] At 09:39 24 March 2015mentioning

confidence: 97%

The cytoskeleton and neurite initiation

2013

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Neurons begin their life as simple spheres, but can ultimately assume an elaborate morphology with numerous, highly arborized dendrites, and long axons. This is achieved via an astounding developmental progression which is dependent upon regulated assembly and dynamics of the cellular cytoskeleton. As neurites emerge out of the soma, neurons break their spherical symmetry and begin to acquire the morphological features that define their structure and function. Neurons regulate their cytoskeleton to achieve changes in cell shape, velocity, and direction as they migrate, extend neurites, and polarize. Of particular importance, the organization and dynamics of actin and microtubules directs the migration and morphogenesis of neurons. This review focuses on the regulation of intrinsic properties of the actin and microtubule cytoskeletons and how specific cytoskeletal structures and dynamics are associated with the earliest phase of neuronal morphogenesis—neuritogenesis.

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“…Factors such as stiffness of the substrate can be important in determining the growth patterns of neurons, as shown by the growth of retinal ganglion cell axons towards softer tissue [42]. Laminin and β-integrin signaling have been found to be important in neuronal polarization and the deletion of β-integrin results in deficits in axonal development [43]. Radial glia, similar to the ridges of the scaffold, provide topographical cues that orientate the migration of embryonic neurons [44].…”

Section: Discussionmentioning

confidence: 99%

Promoting neuronal outgrowth using ridged scaffolds coated with extracellular matrix proteins

Siddiqui

Brunner

Harris

et al. 2019

Preprint

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3Spinal cord injury (SCI) results in cell death, demyelination, and axonal loss. The spinal cord has a 4 limited ability to regenerate and current clinical therapies for SCI are not effective in helping promote 5 neurologic recovery. We have developed a novel scaffold biomaterial that is fabricated from the 6 biodegradable hydrogel oligo[poly(ethylene glycol)fumarate] (OPF). We have previously shown that 7 positively charged OPF scaffolds (OPF+) in an open spaced, multichannel design can be loaded with 8 Schwann cells to support axonal generation and functional recovery following SCI. We have now 9 developed a hybrid OPF+ biomaterial that increases the surface area available for cell attachment and that 10 contains an aligned microarchitecture and extracellular matrix (ECM) proteins to better support axonal 11 regeneration. OPF+ was fabricated as 0.08 mm thick sheets containing 100 μm high polymer ridges that 12 self-assembles into a spiral shape when hydrated. Laminin, fibronectin, or collagen I coating promoted 13 neuron attachment and axonal outgrowth on the scaffold surface. In addition, the ridges aligned axons in 14 a longitudinal bipolar orientation. Decreasing the space between the ridges increased the number of cells 15 and neurites aligned in the direction of the ridge. Schwann cells seeded on laminin coated OPF+ sheets 16 aligned along the ridges over a 6-day period and could myelinate dorsal root ganglion neurons over 4 17 weeks. The OPF+ sheets support axonal regeneration when implanted into the transected spinal cord.18This novel scaffold design, with closer spaced ridges and Schwann cells is a novel biomaterial construct 19 to promote regeneration after SCI. 20The spinal cord has a limited ability to regenerate after spinal cord injury (SCI) and available therapies are 3 not efficacious in promoting recovery of motor and sensory neurological function. The failure to recover 4 function may be due to secondary events that occur after the primary insult such as cell death, axonal loss, 5 demyelination, cyst formation and an increase in the inhibitory microenvironment [1]. Many therapies are 6 currently under investigation for treating one or more of these secondary events using neuroprotective 7 strategies and cell, regenerative, and rehabilitative therapies [1, 2]. A single therapeutic strategy is 8 unlikely to be effective in treating a disorder that is heterogeneous in its underlying pathophysiology. 9Combinatorial treatments that simultaneously address multiple contributions to the residual of the injury 10 will be required. 11Biomaterial scaffolds are an attractive platform for combinatorial therapies because they are able to bridge 12 the physical gap produced from gliosis, cyst formation, and cell death by providing structural support for 13 regenerating cells [3, 4]. Biomaterials can be combined with extracellular matrices, cells, or 14 pharmaceuticals to promote a more hospitable environment for regeneration [3, 5, 6]. We have developed 15 a positively charged polymer, oligo[poly(ethylene gl...

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

Cited by 64 publications

References 74 publications

MicroRNAs in the axon locally mediate the effects of chondroitin sulfate proteoglycans and cGMP on axonal growth

MicroRNAs in the axon locally mediate the effects of chondroitin sulfate proteoglycans and cGMP on axonal growth

The cytoskeleton and neurite initiation

Promoting neuronal outgrowth using ridged scaffolds coated with extracellular matrix proteins

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