YAP and TAZ Regulate Cc2d1b and Purβ in Schwann Cells.

Sophie Belin,Laura M Feltri,Jordan J S Verplank,Yungki Park,Jacob Herron,Yannick Poitelon

doi:10.3389/fnmol.2019.00177

Abstract

Schwann cells (SCs) are exquisitely sensitive to the elasticity of their environment and their differentiation and capacity to myelinate depend on the transduction of mechanical stimuli by YAP and TAZ. YAP/TAZ, in concert with other transcription factors, regulate several pathways including lipid and sterol biosynthesis as well as extracellular matrix receptor expressions such as integrins and G-proteins. Yet, the characterization of the signaling downstream YAP/TAZ in SCs is incomplete. Myelin sheath production by SC coincides with rapid up-regulation of numerous transcription factors. Here, we show that ablation of YAP/TAZ alters the expression of transcription regulators known to regulate SC myelin gene transcription and differentiation. Furthermore, we link YAP/TAZ to two DNA binding proteins, Cc2d1b and Purβ, which have no described roles in myelinating glial cells. We demonstrate that silencing of either Cc2d1b or Purβ limits the formation of myelin segments. These data provide a deeper insight into the myelin gene transcriptional network and the role of YAP/TAZ in myelinating glial cells.

Highlights

The function of the nervous system relies on the ability of peripheral nerve fibers to transmit information to and from the target tissues
In contrast to classical analyses based on gene dysregulation, which would highlight genes highly regulated by YAP/TAZ (Poitelon et al, 2016), we used our dataset to look at DNA binding proteins highly expressed in Yap cHet; Taz cKO sciatic nerves, with the secondary assumption that their level of expression would be correlated to their importance in myelin formation
We were able to identify that most of the genes known to be either activators or inhibitors of myelination are highly expressed in sciatic nerves and are dysregulated in Yap cHet; Taz cKO

Summary

Introduction

The function of the nervous system relies on the ability of peripheral nerve fibers to transmit information to and from the target tissues. SC integrate biochemical signaling pathways and mechanical stimuli coming from the extracellular matrix or from the axon (Michailov et al, 2004; Feltri and Wrabetz, 2005; Taveggia et al, 2005; Belin et al, 2017). These signals regulate an intricate network of transcription factors that control differentiation of SCs and myelination (e.g., EGR2, YY1, ZEB2, Topilko et al, 1994; Nagarajan et al, 2001; He et al, 2010; Weng et al, 2012; Quintes et al, 2016; Wu et al, 2016).

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Conclusion