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The evolution of Olig genes and their roles in myelination.

ABSTRACT: One of the special attributes of vertebrates is their myelinated nervous system. By increasing the conduction velocity of axons, myelin allows for increased body size, rapid movement and a large and complex brain. In the central nervous system (CNS), oligodendrocytes (OLs) are the myelin-forming cells. The transcription factors OLIG1 and OLIG2, master regulators of OL development, presumably also played a seminal role during the evolution of the genetic programme leading to myelination in the CNS. From the available ontogenetic and phylogenetic data we attempt to reconstruct the evolutionary events that led to the emergence of the Olig gene family and speculate about the links between Olig genes, their specific cis-regulatory elements and myelin evolution. In addition, we report a putative myelin basic protein (MBP) ancestor in the lancelet Branchiostoma floridae, which lacks compact myelin. The lancelet 'Mbp' gene lacks the OLIG1/2- and SOX10-binding sites that characterize vertebrate Mbp homologs, raising the possibility that insertion of cis-regulatory elements might have been involved in evolution of the myelinating programme.

SUBMITTER: Li H

PROVIDER: S-EPMC6326352 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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The evolution of Olig genes and their roles in myelination.

Li Huiliang H Richardson William D WD

Neuron glia biology 20080501 2

One of the special attributes of vertebrates is their myelinated nervous system. By increasing the conduction velocity of axons, myelin allows for increased body size, rapid movement and a large and complex brain. In the central nervous system (CNS), oligodendrocytes (OLs) are the myelin-forming cells. The transcription factors OLIG1 and OLIG2, master regulators of OL development, presumably also played a seminal role during the evolution of the genetic programme leading to myelination in the CN ...[more]

PMID: 19737433

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Project description:BackgroundAxonal myelination is critical for the functioning of vertebrate nervous system. Myelin sheath malformation or degeneration can cause a variety of neurological diseases. Our previous study identified multiple potential myelination-related transcriptional factors (TFs), including expressed sequence tag (ETS) variant transcription factor 1 (Etv1)/Er81, via gene microarray analysis of Schwann cells (SCs) at various myelination stages. Etv1 is known to be involved in the regulation of neuronal specialization, muscle spindle differentiation, and sensorimotor connectivity. However, to our knowledge, to date, there are no relevant studies that Etv1 regulates SC myelination.MethodsTo investigate the roles of Etv1 in SC re-myelination, an in vivo mouse myelination model was used, in which the sciatic nerve is crushed. Etv1 in nerves was knocked down via in situ injection of cholesterol-modified Etv1-small interfering (si)RNA. The expression of myelin-associated glycoprotein (MAG) was evaluated by Western blotting (WB) and immunohistochemistry (IHC). Myelination was assessed by transmission electron microscopy (TEM). The effects of Etv1 on SC proliferation, migration, and differentiation were assessed in vitro using the EdU cell proliferation kit, a culture-insert scratch assay, a SC aggregate sphere migration assay on the axons of dorsal root ganglions (DRGs), and a SC differentiation model. Chromatin immunoprecipitation (ChIP) united with quantitative real-time PCR (qPCR), known as ChIP-qPCR, and luciferase activity reporter assays were performed to explore the possible mechanisms by which Etv1 controls SC differentiation and myelination.ResultsThe results demonstrated that Etv1 promoted myelination by facilitating SC proliferation, migration, and differentiation. Etv1 expression in SCs was upregulated during re-myelination, and knocking down Etv1 expression dramatically abrogated SC re-myelination in the crushed sciatic nerves. Moreover, silencing of Etv1 by siRNA in SCs in vitro inhibited its migration, proliferation, and differentiation. The results of ChIP-qPCR and luciferase reporter assay showed that Etv1 may regulate SC differentiation and myelination by binding to the promoters of myelination-related genes, such as MAG and Runx2, to initiate their transcription.ConclusionsTaken together, these findings demonstrated a previously unknown role of Etv1 in SC differentiation and myelination, providing a candidate molecular target for clinical interventions in demyelinating diseases.

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The evolution of Olig genes and their roles in myelination.

Publications

The evolution of Olig genes and their roles in myelination.

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