Role of the Pbrm1 subunit and the PBAF complex in Schwann cell development

Vanessa Polanetzki,Tina Baroti,Michael Wegner,Ernst R Tamm,Margit Schimmel,Franziska Fröb

doi:10.1038/s41598-022-06588-8

Vanessa Polanetzki, Tina Baroti + Show 4 more

Open Access

https://doi.org/10.1038/s41598-022-06588-8

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Abstract

Myelin sheath formation in the peripheral nervous system and the ensuing saltatory conduction rely on differentiated Schwann cells. We have previously shown that transition of Schwann cells from an immature into a differentiated state requires Brg1 that serves as the central energy generating subunit in two related SWI/SNF-type chromatin remodelers, the BAF and the PBAF complex. Here we used conditional deletion of Pbrm1 to selectively interfere with the PBAF complex in Schwann cells. Despite efficient loss of Pbrm1 early during lineage progression, we failed to detect any substantial alterations in the number, proliferation or survival of immature Schwann cells as well as in their rate and timing of terminal differentiation. As a consequence, postnatal myelin formation in peripheral nerves appeared normal. There were no inflammatory alterations in the nerve or other signs of a peripheral neuropathy. We conclude from our study that Pbrm1 and very likely the PBAF complex are dispensable for proper Schwann cell development and that Schwann cell defects previously observed upon Brg1 deletion are mostly attributable to altered or absent function of the BAF complex.

Highlights

Myelin sheath formation in the peripheral nervous system and the ensuing saltatory conduction rely on differentiated Schwann cells
Schwann cells represent the main population of glial cells in the peripheral nervous system (PNS) and line axons in the peripheral nerves as myelinating or non-myelinating Schwann cells
SWI/SNF-type remodelers are intrinsically heterogeneous in their subunit composition and are frequently grouped into BAF and PBAF complexes in v ertebrates[8]

Summary

Introduction

Myelin sheath formation in the peripheral nervous system and the ensuing saltatory conduction rely on differentiated Schwann cells. We have previously shown that transition of Schwann cells from an immature into a differentiated state requires Brg[1] that serves as the central energy generating subunit in two related SWI/SNF-type chromatin remodelers, the BAF and the PBAF complex. Schwann cells represent the main population of glial cells in the peripheral nervous system (PNS) and line axons in the peripheral nerves as myelinating or non-myelinating Schwann cells Their development from the neural crest is coordinated by combinatorially acting, continuously present or stage-specific transcription factors that form an evolving gene regulatory network in cooperation with regulatory RNAs and various classes of chromatin-modifying proteins or complexes, such as histone modifying enzymes, DNA methyltransferases and chromatin remodeling c omplexes[1–4]. In case of the SWI/ SNF-type remodelers, we previously deleted the ATP-hydrolyzing Brg[1] subunit in the late Schwann cell precursor stage and observed a radial sorting defect. Considering that all essential and constitutive subunits of BAF and PBAF complexes occur in developing Schwann cells[1,13,14] it is currently not clear, to what extent the previously observed defects in Schwann cell development after Brg[1] deletion are due to impaired function of the Brg1-containing BAF complex as opposed to the Brg1-containing PBAF complex

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