CNS myelination requires cytoplasmic dynein function

Abstract

Background Cytoplasmic dynein provides the main motor force for minus-end-directed transport of cargo on microtubules. Within the vertebrate central nervous system (CNS), proliferation, neuronal migration and retrograde axon transport are among the cellular functions known to require dynein. Accordingly, mutations of DYNC1H1, which encodes the heavy chain subunit of cytoplasmic dynein, have been linked to developmental brain malformations and axonal pathologies. Oligodendrocytes, the myelinating glial cell type of the CNS, migrate from their origins to their target axons and subsequently extend multiple long processes that ensheath axons with specialized insulating membrane. These processes are filled with microtubules, which facilitate molecular transport of myelin components. However, whether oligodendrocytes require cytoplasmic dynein to ensheath axons with myelin is not known. Results We identified a mutation of zebrafish dync1h1 in a forward genetic screen that caused a deficit of oligodendrocytes. Using in vivo imaging and gene expression analyses, we additionally found evidence that dync1h1 promotes axon ensheathment and myelin gene expression. Conclusions In addition to its well known roles in axon transport and neuronal migration, cytoplasmic dynein contributes to neural development by promoting myelination.

Genomic and phenotypic signatures of climate adaptation in anAnolislizard

“…Clinical relevance was obtained from OMIM and PubMed, both for animal model and human. Table references (superscript numbers): (1) Yoon et al., ; (2) Yang et al., ; (3) Myers et al., ; (4) Estrada et al., . *Not in Interactome.…”

Mice lacking BCAS1, a novel myelin‐associated protein, display hypomyelination, schizophrenia‐like abnormal behaviors, and upregulation of inflammatory genes in the brain

“…Considering that BCAS1 can bind to DLC directly (Ninomiya et al, 2005), BCAS1 probably maintains the stability of DLC by this action. As DLC is a subunit of dynein and myosin Va (Espindola et al, 2000;Wickstead & Gull, 2007), the loss of DLC may induce dysfunction of molecular transport in oligodendrocytes and subsequent hypomyelination, as described in some reports (Langworthy & Appel, 2012;Yang et al, 2015).…”

Axoglial Adhesion by Cadm4 Regulates CNS Myelination

“…Mice were anaesthetized and perfused with a fixative containing 4% PFA, 2.5% glutaraldehyde and 0.1M cacodylate buffer. Brains and spinal cords were isolated and incubated in the fixative overnight at room temperature and processed as previously described (Yang et al, 2015). Samples were examined using a Tecnai Spirit or T12 transmission electron microscope, equipped with a FEI Eagle camera or a Gatan ES500W Erlangshen camera respectively.…”