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Sox2-dependent fibronectin fibrillogenesis controls directional collective migration of Schwann cells

ABSTRACT: The extracellular matrix is essential for tissue formation and regeneration through the control of cellular behavior. Deregulation of extracellular matrix components is associated to disease, including neurodegeneration. After peripheral nerve injury, Schwann cells guide regrowing axons to their targets. These glial cells migrate collectively and provide an extracellular environment to enable neural repair. How this occurs remains poorly understood. Here, we show that Sox2 controls fibronectin fibrillogenesis in Schwann cells to provide a highly oriented extracellular matrix, which supports their rapid collective migration with a continuous cellular flow. Sox2 directly activates fibronectin expression in Schwann cells, leading to an increase in fibrillogenesis and cellular huddling. Accordingly, loss of fibrillogenesis leads to glial disassembly and disorganized axon regrowth. In vivo, 7 days post nerve injury, we found that pro-regenerative Schwann cells co-express Sox2 and the EIIIA-containing fibronectin splicing isoform. This mechanism is conserved in mammals, including humans, but absent in zebrafish. Taken together, our results demonstrate that Sox2 directly controls fibrillogenesis and provide a novel mechanism for the modification of the environmental architecture by glial cells during neuronal repair.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE94590 | GEO | 2020/02/11

REPOSITORIES: GEO

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Rattus norvegicus

Project description:Sox2-dependent fibronectin fibrillogenesis controls directional collective migration of Schwann cells

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Initiation of fibronectin fibrillogenesis is an enzyme-dependent process

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2023-04-17 | PXD040900 | Pride

Initiation of fibronectin fibrillogenesis is an enzyme-dependent process

2023-04-17 | PXD040505 | Pride

Adipo-glial signaling mediates metabolic adaptation in peripheral nerve regeneration

Project description:The peripheral nervous system harbours a remarkable potential to regenerate after acute nerve trauma. Full functional recovery, however, is rare and critically depends on peripheral nerve Schwann cells that orchestrate break down and resynthesis of myelin and, at the same time, support axonal regrowth. How Schwann cells meet the high metabolic demand required for nerve repair remains poorly understood. We here report that nerve injury induces adipocyte to glial signaling, and identify the adipokine leptin as an upstream regulator of glial metabolic adaptation in regeneration. Signal integration by leptin receptors in Schwann cells ensures efficient peripheral nerve repair by adjusting injury-specific catabolic processes in regenerating nerves, including myelin autophagy and mitochondrial respiration. Our findings propose a model according to which acute nerve injury triggers a therapeutically targetable intercellular crosstalk that modulates glial metabolism, to provide sufficient energy for successful nerve repair.

2023-12-12 | GSE244328 | GEO

Single-cell RNA-seq reveals the difference between Schwann cells in dorsal root ganglion and sciatic nerve

Project description:Schwann cells are important glial cells in peripheral nervous system. In this study, we performed single cell RNA-sequencing (scRNA-seq) analysis of Schwann cells exist in both dorsal root ganglion(DRG) and sciatic nerve.We categorized DRG and sciatic nerve Schwann cells into different subtypes,and found common subtypes and different subtypes.In addition, we discovered the proliferation and migration ability of Schwann cells were distinct in different tissues.Our current study revealed the distinctive characteristics of Schwann cells in DRG and sciatic nerve.

2023-03-26 | GSE147615 | GEO

FOSL1 modulates Schwann cell responses in the wound microenvironment and regulates peripheral nerve regeneration

Project description:Peripheral glial Schwann cells switch to a repair state after nerve injury, proliferate to supply lost cell population, migrate to form regeneration tracks, and generates a permissive microenvironment for nerve regeneration. Exploring essential regulators of the repair responses of Schwann cells may benefit the clinical treatment for peripheral nerve injury. In the present study, FOSL1 regulates Schwann cell phenotype modulation and provided a novel therapeutic approach to orchestrate the regeneration and functional recovery of injured peripheral nerves.

2022-10-02 | GSE214449 | GEO

Multipotent Peripheral Glial Cells Generate Neuroendocrine Cells of the Adrenal Medulla

Project description:Cells producing adrenalin are largely derived from nerve-associated Schwann cell precursors via an intermediate progenitor “bridge” cell. We demonstrate that large numbers of chromaffin cells arise from peripheral glial stem cells, termed Schwann cell precursors (SCPs)

2017-07-10 | GSE99933 | GEO

Transcriptional profiles of neural crest-derived progenitor cells from the small bowel and subcutaneous adipose tissue

Project description:Neural stem cells (NSCs) are most commonly sourced from neural tissue such as the central nervous system or the enteric nervous system (ENS) of the gut. Emerging evidence has shown that adipose tissue contains its own complex nervous system consisting of sympathetic and sensory innervation. The entirety of the peripheral nervous system is the progeny of Wnt1-expressing cells of the embryonic neural crest. This includes the ENS, autonomic neurons, and Schwann cell precursors that provide peripheral glial cells. Counterintuitive to their name, however, embryonic Schwann cell precursors represent multipotent stem cells that migrate along embryonic nerve fibers and contribute to glial and non-glial cell populations, including melanocytes, neuroendocrine chromaffin cells, enteric neurons, sympathetic neurons and mesenchymal stem cells from the bone marrow, depending on local environmental cues. However, no equivalent progenitors are known to exist postnatally in the nerve fiber niche. Schwann cells have been demonstrated to give rise to enteric neurons postnatally, suggesting they retain neuronal progenitor properties and offer a potential source of NSCs for regenerative therapies. In this study, we compare the transcriptomic properties of neural crest-derived NSCs from the intestine (enteric neural progenitors) and the nerve fibers of the subcutaneous adipose tissue and evaluate the effects of different methods of NSC culture and isolation.

2022-05-31 | GSE200689 | GEO

Tensin3 interaction with talin drives formation of fibronectin-associated fibrillar adhesions

Project description:The formation of healthy tissue involves continuous remodelling of the extracellular matrix (ECM). Whilst it is known that this requires integrin-associated cell-ECM adhesion sites (CMAs) and actomyosin-mediated forces, the underlying mechanisms remain unclear. Here we examine how tensin3 contributes to formation of fibrillar adhesions (FBs) and fibronectin fibrillogenesis. Using BioID mass spectrometry and a mitochondrial targeting assay, we establish that tensin3 associates with the mechanosensors talin and vinculin. We show that the talin R11 rod domain binds directly to a helical motif within the central intrinsically disordered region (IDR) of tensin3, whilst vinculin binds indirectly to tensin3 via talin. Using CRISPR knock-out cells in combination with defined tensin3 mutations, we show (i) that tensin3 is critical for formation of alpha5 beta1-integrin FBs and for fibronectin fibrillogenesis, and (ii) the talin/tensin3 interaction drives this process, with vinculin acting to potentiate it.

2022-09-09 | PXD026343 | Pride

Genome-wide analysis of Schwann cell gene expression in LKB1-SCKO mutant mice prior to occurrence of axon degeneration

Project description:Analysis of gene expression in LKB1(Stk11)-depleted sciatic nerves (LKB1-SCKO) vs control nerves from age-matched mice. Gene expression profiles are predominantly derived from Schwann cell glia and provide important information about the response of peripheral nerve Schwann cells to inactivation of the metabolic regulator protein LKB1(aka Stk11). Total RNA obtained from sciatic nerve segments from 6 LKB1-SCKO mutant mice compared to RNA from nerve segments from 6 control mice (floxed LKB1 mutant mice that do not express Cre recombinase).

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