[Epub ahead of print]

Jmy regulates oligodendrocyte differentiation via modulation of actin cytoskeleton dynamics

Maria M. Azevedo, Helena S. Domingues, Fabrice P. Cordelières, Paula Sampaio, Ana I. Seixas, João B. Relvas
Glia. 2018-05-06; :
DOI: 10.1002/glia.23342

Read on PubMed

Jmy regulates oligodendrocyte differentiation via modulation of actin
cytoskeleton dynamics.

Azevedo MM(1)(2), Domingues HS(1)(2), Cordelières FP(3), Sampaio P(1)(2), Seixas
AI(1)(2), Relvas JB(1)(2)(4).

Author information:
(1)i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto,
Porto, Portugal.
(2)IBMC – Instituto de Biologia Molecular e Celular, Porto, Portugal.
(3)Bordeaux Imaging Centre, UMS 3420 CNRS, CNRS-INSERM, University of Bordeaux,
Bordeaux, France.
(4)The Discoveries Centre for Regeneration and Precision Medicine, Porto campus,
Porto, Portugal.

During central nervous system development, oligodendrocytes form structurally and
functionally distinct actin-rich protrusions that contact and wrap around axons
to assemble myelin sheaths. Establishment of axonal contact is a limiting step in
myelination that relies on the oligodendrocyte’s ability to locally coordinate
cytoskeletal rearrangements with myelin production, under the control of a
transcriptional differentiation program. The molecules that provide fine-tuning
of actin dynamics during oligodendrocyte differentiation and axon ensheathment
remain largely unidentified. We performed transcriptomics analysis of soma and
protrusion fractions from rat brain oligodendrocyte progenitors and found a
subcellular enrichment of mRNAs in newly-formed protrusions. Approximately 30% of
protrusion-enriched transcripts encode proteins related to cytoskeleton dynamics,
including the junction mediating and regulatory protein Jmy, a multifunctional
regulator of actin polymerization. Here, we show that expression of Jmy is
upregulated during myelination and is required for the assembly of actin
filaments and protrusion formation during oligodendrocyte differentiation.
Quantitative morphodynamics analysis of live oligodendrocytes showed that
differentiation is driven by a stereotypical actin network-dependent “cellular
shaping” program. Disruption of actin dynamics via knockdown of Jmy leads to a
program fail resulting in oligodendrocytes that do not acquire an arborized
morphology and are less efficient in contacting neurites and forming myelin wraps
in co-cultures with neurons. Our findings provide new mechanistic insight into
the relationship between cell shape dynamics and differentiation in development.

© 2018 Wiley Periodicals, Inc.

DOI: 10.1002/glia.23342
PMID: 29732611

Know more about