Jmy regulates oligodendrocyte differentiation via modulation of actin cytoskeleton dynamics

• Tipo: Artigo em Revista Científica Internacional
• Data: 2018

Autores

Azevedo, MM (Autor) Outra; Domingues, HS (Autor) Outra; Cordelieres, FP (Autor) Outra; Sampaio, P (Autor) Outra; Seixas, AI (Autor) Outra; Relvas, JB (Autor) ICBAS

Revista

Título: GLIA

Vol. 66

Páginas: 1826-1844

ISSN: 0894-1491

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 13 Citações

Scopus - 12 Citações

Outras Informações

ID Authenticus: P-00P-R8D

DOI: 10.1002/glia.23342

Abstract (EN): 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 19