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PMID:16723544

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Citation

Kim, HJ, DiBernardo, AB, Sloane, JA, Rasband, MN, Solomon, D, Kosaras, B, Kwak, SP and Vartanian, TK (2006) WAVE1 is required for oligodendrocyte morphogenesis and normal CNS myelination. J. Neurosci. 26:5849-59

Abstract

Myelin formation involves the outgrowth of an oligodendrocyte cell process that can be regarded as a giant lamellipodium because it is an actively growing structure with extruded cytoplasm. The actin cytoskeleton is critical to morphogenesis, but little is known about regulation of actin dynamics in oligodendrocytes. Wiskott-Aldrich syndrome protein family verprolin homologous (WAVE) proteins mediate lamellipodia formation; thus, we asked whether these proteins function in oligodendrocyte process formation and myelination. Here, we show that WAVE1 is expressed by oligodendrocytes and localizes to the lamella leading edge where actin polymerization is actively regulated. CNS WAVE1 expression increases at the onset of myelination. Expression of dominant-negative WAVE1 impaired process outgrowth and lamellipodia formation in cultured oligodendrocytes. Similarly, oligodendrocytes isolated from mice lacking WAVE1 had fewer processes compared with controls, whereas neurons and astrocytes exhibited normal morphology. In white matter of WAVE1-/- mice, we found regional hypomyelination in the corpus callosum and to a lesser extent in the optic nerve. In optic nerve from WAVE1-/- mice, there were fewer nodes of Ranvier but nodal morphology was normal, implicating a defect in myelin formation. Our in vitro findings support a developmentally dynamic and cell-autonomous role for WAVE1 in regulating process formation in oligodendrocytes. Additionally, WAVE1 function during CNS myelination appears to be linked to regional cues. Although its loss can be compensated for in many CNS regions, WAVE1 is clearly required for normal amounts of myelin to form in corpus callosum and optic nerve. Together, these data demonstrate a role for WAVE1 in oligodendrocyte morphogenesis and myelination.

Links

PubMed Online version:10.1523/JNEUROSCI.4921-05.2006

Keywords

Animals; Animals, Newborn; Brain/cytology; Brain/metabolism; Cells, Cultured; Mice; Morphogenesis/physiology; Nerve Fibers, Myelinated/metabolism; Nerve Fibers, Myelinated/ultrastructure; Oligodendroglia/cytology; Oligodendroglia/metabolism; Rats; Rats, Sprague-Dawley; Wiskott-Aldrich Syndrome Protein Family/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SCN2A

located_in

GO:0033270: paranode region of axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:MBP

located_in

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000128)

Seeded From UniProt

complete

MOUSE:NFASC

located_in

GO:0033270: paranode region of axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:WASF3

acts_upstream_of_or_within

GO:0030032: lamellipodium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000128)

Seeded From UniProt

complete

MOUSE:WASF3

acts_upstream_of_or_within

GO:0031643: positive regulation of myelination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WASF3

acts_upstream_of_or_within

GO:0031643: positive regulation of myelination

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2663235

P

Seeded From UniProt

complete

MOUSE:WASF3

acts_upstream_of_or_within

GO:0014003: oligodendrocyte development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2663235

P

Seeded From UniProt

complete

MOUSE:WASF3

located_in

GO:0030027: lamellipodium

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000128)

Seeded From UniProt

complete

MOUSE:MBP

part_of

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000128)

Seeded From UniProt

complete


See also

References

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