The Hippo pathway: Horizons for innovative treatments of peripheral nerve diseases

Feltri, M. Laura; Weaver, Michael; Belin, Sophie; Poitelon, Yannick

doi:10.1111/jns.12431

Cited by 14 publications

(15 citation statements)

References 202 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have also established that PIEZO1 contributes to the regulation of YAP/TAZ in myelinating cells. Defects of myelination in the PNS are starting to be associated with mechanobiology in demyelinating diseases (i.e., traumatic and inherited) as well as tumors (for review, see Acheta et al, 2021;Feltri et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Piezo channels contribute to the regulation of myelination in Schwann cells

Acheta

Bhatia

Jeanette

et al. 2022

Glia

Self Cite

View full text Add to dashboard Cite

Peripheral nerves and Schwann cells have to sustain constant mechanical constraints, caused by developmental growth as well as stretches associated with movements of the limbs and mechanical compressions from daily activities. In Schwann cells, signaling molecules sensitive to stiffness or stretch of the extracellular matrix, such as YAP/TAZ, have been shown to be critical for Schwann cell development and peripheral nerve regeneration. YAP/TAZ have also been suggested to contribute to tumorigenesis, neuropathic pain, and inherited disorders. Yet, the role of mechanosensitive ion channels in myelinating Schwann cells is vastly unexplored. Here we comprehensively assessed the expression of mechanosensitive ion channels in Schwann cells and identified that PIEZO1 and PIEZO2 are among the most abundant mechanosensitive ion channels expressed by Schwann cells. Using classic genetic ablation studies, we show that PIEZO1 is a transient inhibitor of radial and longitudinal myelination in Schwann cells. Contrastingly, we show that PIEZO2 may be required for myelin formation, as the absence of PIEZO2 in Schwann cells delays myelin formation. We found an epistatic relationship between PIEZO1 and PIEZO2, at both the morphological and molecular levels. Finally, we show that PIEZO1 channels affect the regulation of YAP/TAZ activation in Schwann cells. Overall, we present here the first demonstration that PIEZO1 and PIEZO2 contribute to mechanosensation in Schwann cells as well myelin development in the peripheral nervous system.

show abstract

Section: Discussionmentioning

confidence: 99%

Piezo channels contribute to the regulation of myelination in Schwann cells

Acheta

Bhatia

Jeanette

et al. 2022

Glia

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, Schwann cells wrap and produce myelin so that internodal length and myelin thickness are proportioned to axonal diameter [1,13]. As described before, the Hippo pathway and their activators such as for instance Crb3 and NF2, limit longitudinal myelin growth and internodal length by YAP/TAZ phosphorylation and inactivation (cytoplasmic retention) [97]. Concerning radial myelin growth and thickness, several negative regulators have been identified most of them converging on the NRG1 pathway [1].…”

Section: Negative Regulators Of Schwann Cell Myelinationmentioning

confidence: 91%

“…YAP/TAZ. Transcription co-activator Yes-associated protein 1 (YAP) and its coactivator with PDZ-binding domain (TAZ) are key promoters of myelination, recently reviewed in Feltri et al [97]. YAP/TAZ can be phosphorylated and localized in the cytosol, or viceversa, not phosphorylated and translocate in the nucleus, promoting transcription by binding to TEAD (TEA domain transcription factor) transcription factors.…”

Section: Schwann Cell Transduction Of Extrinsic Pro-myelinating Signalsmentioning

confidence: 99%

Myelin Biology

Bolino

2021

Neurotherapeutics

View full text Add to dashboard Cite

Myelin is a key evolutionary specialization and adaptation of vertebrates formed by the plasma membrane of glial cells, which insulate axons in the nervous system. Myelination not only allows rapid and efficient transmission of electric impulses in the axon by decreasing capacitance and increasing resistance but also influences axonal metabolism and the plasticity of neural circuits. In this review, we will focus on Schwann cells, the glial cells which form myelin in the peripheral nervous system. Here, we will describe the main extrinsic and intrinsic signals inducing Schwann cell differentiation and myelination and how myelin biogenesis is achieved. Finally, we will also discuss how the study of human disorders in which molecules and pathways relevant for myelination are altered has enormously contributed to the current knowledge on myelin biology.

show abstract

“…Another pathway regulated by ECM signals (primarily the stiffness of the extracellular environment) and important for SC polarity is the Hippo pathway, which mainly acts through the activation/inactivation of YAP and TAZ molecules, reviewed in Feltri et al [100]. The Hippo pathway controls the cytoplasmic-nuclear shuttling of YAP/TAZ.…”

Section: Radial Sorting From the Schwann Cell Point Of Viewmentioning

confidence: 99%

“…Laminins likely inhibit the Hippo pathway, activating YAP/ TAZ through mechanoreceptors such as integrins. Interestingly, deletion of TAZ causes moderate radial sorting arrest, while YAP alone does not but it enhances sorting defect in double mutant with TAZ, suggesting that these molecules regulate radial sorting likely through the control of SC proliferation and differentiation by promoting transcription of laminin receptors, ERB2/3, ZEB2, and other molecules [100][101][102][103].…”

Section: Radial Sorting From the Schwann Cell Point Of Viewmentioning

confidence: 99%

Peripheral Nerve Development and the Pathogenesis of Peripheral Neuropathy: the Sorting Point

Previtali

2021

Neurotherapeutics

View full text Add to dashboard Cite

Nerve development requires a coordinated sequence of events and steps to be accomplished for the generation of functional peripheral nerves to convey sensory and motor signals. Any abnormality during development may result in pathological structure and function of the nerve, which evolves in peripheral neuropathy. In this review, we will briefly describe different steps of nerve development while we will mostly focus on the molecular mechanisms involved in radial sorting of axons, one of these nerve developmental steps. We will summarize current knowledge of molecular pathways so far reported in radial sorting and their possible interactions. Finally, we will describe how disruption of these pathways may result in human neuropathies.

show abstract

The Hippo pathway: Horizons for innovative treatments of peripheral nerve diseases

Cited by 14 publications

References 202 publications

Piezo channels contribute to the regulation of myelination in Schwann cells

Piezo channels contribute to the regulation of myelination in Schwann cells

Myelin Biology

Peripheral Nerve Development and the Pathogenesis of Peripheral Neuropathy: the Sorting Point

Contact Info

Product

Resources

About