Jab1 regulates Schwann cell proliferation and axonal sorting through p27

Porrello, Emanuela; Rivellini, Cristina; Dina, Giorgia; Triolo, Daniela; Carro, Ubaldo Del; Ungaro, Daniela; Panattoni, Martina; Feltri, M. Laura; Wrabetz, Lawrence; Pardi, Ruggero; Quattrini, Angelo; Previtali, Stefano C.

doi:10.1084/jem.20130720

Cited by 34 publications

(39 citation statements)

References 52 publications

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“…Ultrathin sections were prepared using an ultramicrotome and stained with uranyl acetate and lead citrate for transmission electron microscopy (Hitachi H-7100 Hitachi Co. Ltd., Tokyo, Japan) at 80 kV. G ratios, namely the ratio of the mean inner diameter of an axon to the mean diameter of the fiber (including myelin), were calculated as described (26,27). Sciatic nerve myelination, de-myelination, and re-myelination were assessed by electron microscopy, as described previously (28).…”

Section: Methodsmentioning

confidence: 99%

Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation

Tashiro

Hasegawa

et al. 2015

Journal of Biological Chemistry

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Background: Factors that govern peripheral neuropathy associated with Schwann cell dysfunction are not fully understood. Results: Under hyperglycemic conditions, Schwann cells de-differentiate into immature cells via sorbitol accumulation and Igf1 down-regulation. Conclusion: Schwann cell de-differentiation promotes neuropathy development under hyperglycemic conditions. Significance: These findings reveal new mechanisms underlying neuropathy seen in diabetes mellitus via Schwann cell de-differentiation leading to de-myelination.

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Section: Methodsmentioning

confidence: 99%

Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation

Tashiro

Hasegawa

et al. 2015

Journal of Biological Chemistry

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“…Interestingly, absence of non-coding RNAs due to deletion of dicer in Schwann cells delays radial sorting, (Pereira and others, 2010; Yun and others, 2010) but it is unclear which microRNAs are involved and which target they might regulate. Curiously, there is no information at the moment on transcription factors that influence radial sorting, but nuclear control of sorting is likely important, as deletion of Hdac1 and Jab1 (see also below) delays radial sorting (Jacob and others, 2011; Porrello and others, 2014). …”

Section: Molecular Mechanisms Of Radial Sortingmentioning

confidence: 99%

“…The myelin periodicity of polyaxonal bundles is comparable to that of normal myelinated fibers, and myelin thickness might be normal or reduced. Polyaxonal myelination is a rare feature in normal nerves, and usually limited to the early postnatal developmental period; instead it is observed quite often in mature nerves of many mouse mutants, such as those for Laminins 211, 411, where it is associated with reduced proliferation, and it was also recently described in mice with Schwann cell conditional deletion of the nuclear protein Jab1 (Brown and Radich, 1979; Porrello and others, 2014; Wallquist and others, 2005; Yang and others, 2005). Loss of Jab1 in Schwan cells is associated with abnormal p27 levels, arrest in cell cycle and aberrant differentiation.…”

Section: Control Of Schwann Cell Proliferation Exit From the Cell Cymentioning

confidence: 99%

How Schwann Cells Sort Axons

Feltri¹,

Poitelon²,

2015

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Peripheral nerves contain large myelinated and small unmyelinated (Remak) fibers that perform different functions. The choice to myelinate or not is dictated to Schwann cells by the axon itself, based on the amount of Neuregulin I-type III exposed on its membrane. Peripheral axons are more important in determining the final myelination fate than central axons, and the implications for this difference in Schwann cells and oligodendrocytes are discussed. Interestingly, this choice is reversible during pathology, accounting for the remarkable plasticity of Schwann cells, and contributing to the regenerative potential of the peripheral nervous system. Radial sorting is the process by which Schwann cells choose larger axons to myelinate during development. This crucial morphogenetic step is a prerequisite for myelination and for differentiation of Remak fibers, and is arrested in human diseases due to mutations in genes coding for extracellular matrix and linkage molecules. In this review we will summarize progresses made in the last years by a flurry of reverse genetic experiments in mice and fish. This work revealed novel molecules that control radial sorting, and contributed unexpected ideas to our understanding of the cellular and molecular mechanisms that control radial sorting of axons.

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“…Apc lox/lox ;P0-Cre mice exhibit hindlimb clenching when suspended by the tail, a common indication of neurological dysfunction (Golan et al, 2013;Novak et al, 2011;Porrello et al, 2014) (Fig. 1D), and they also suffer from hindlimb weakness as detected by grip strength analysis (Fig.…”

Section: Introductionmentioning

confidence: 99%

Adenomatous polyposis coli regulates radial axonal sorting and myelination in the PNS

et al. 2016

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The tumor suppressor protein adenomatous polyposis coli (APC) is multifunctional -it participates in the canonical Wnt/β-catenin signal transduction pathway as well as modulating cytoskeleton function. Although APC is expressed by Schwann cells, the role that it plays in these cells and in the myelination of the peripheral nervous system (PNS) is unknown. Therefore, we used the Cre-lox approach to generate a mouse model in which APC expression is specifically eliminated from Schwann cells. These mice display hindlimb weakness and impaired axonal conduction in sciatic nerves. Detailed morphological analyses revealed that APC loss delays radial axonal sorting and PNS myelination. Furthermore, APC loss delays Schwann cell differentiation in vivo, which correlates with persistent activation of the Wnt signaling pathway and results in perturbed extension of Schwann cell processes and disrupted lamellipodia formation. In addition, APC-deficient Schwann cells display a transient diminution of proliferative capacity. Our data indicate that APC is required by Schwann cells for their timely differentiation to mature, myelinating cells and plays a crucial role in radial axonal sorting and PNS myelination.

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Jab1 regulates Schwann cell proliferation and axonal sorting through p27

Abstract: Jab1 constitutes a regulatory molecule that integrates laminin211 signals in Schwann cells to govern cell cycle, cell number, and differentiation.

Cited by 34 publications

References 52 publications

Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation

Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation

How Schwann Cells Sort Axons

Adenomatous polyposis coli regulates radial axonal sorting and myelination in the PNS

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