PUBLICATION
nkx2.2a promotes specification and differentiation of a myelinating subset of oligodendrocyte lineage cells in zebrafish
- Authors
- Kucenas, S., Snell, H., and Appel, B.
- ID
- ZDB-PUB-110110-1
- Date
- 2008
- Source
- Neuron glia biology 4(2): 71-81 (Journal)
- Registered Authors
- Appel, Bruce, Kucenas, Sarah, Snell, Heather
- Keywords
- Olig2, zebrafish, neural precursors, glia
- MeSH Terms
-
- Body Patterning/physiology*
- Cell Division/physiology
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism*
- Zebrafish Proteins/metabolism
- Animals, Genetically Modified
- Myelin Sheath/physiology*
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism
- Oligodendroglia/cytology*
- Oligodendroglia/metabolism
- Zebrafish/embryology*
- Animals
- Cell Differentiation/physiology*
- Stem Cells/cytology*
- Stem Cells/metabolism
- Transcription Factors/deficiency
- Transcription Factors/genetics
- Transcription Factors/metabolism*
- Oligonucleotides, Antisense
- Basic Helix-Loop-Helix Transcription Factors/metabolism
- Nerve Tissue Proteins/metabolism
- Cell Lineage
- Spinal Cord/cytology
- Spinal Cord/embryology
- PubMed
- 19737431 Full text @ Neuron Glia Biol.
Citation
Kucenas, S., Snell, H., and Appel, B. (2008) nkx2.2a promotes specification and differentiation of a myelinating subset of oligodendrocyte lineage cells in zebrafish. Neuron glia biology. 4(2):71-81.
Abstract
During development, multipotent neural precursors give rise to oligodendrocyte progenitor cells (OPCs), which migrate and divide to produce additional OPCs. Near the end of embryogenesis and during postnatal stages, many OPCs stop dividing and differentiate as myelinating oligodendrocytes, whereas others persist as nonmyelinating cells. Investigations of oligodendrocyte development in mice indicated that the Nkx2.2 transcription factor both limits the number of OPCs that are formed and subsequently promotes their differentiation, raising the possibility that Nkx2.2 plays a key role in determining myelinating versus nonmyelinating fate. We used in vivo time-lapse imaging and loss-of-function experiments in zebrafish to further explore formation and differentiation of oligodendrocyte lineage cells. Our data show that newly specified OPCs are heterogeneous with respect to gene expression and fate. Whereas some OPCs express the nkx2.2a gene and differentiate as oligodendrocytes, others that do not express nkx2.2a mostly remain as nonmyelinating OPCs. Similarly to mouse, loss of nkx2.2a function results in excess OPCs and delayed oligodendrocyte differentiation. Notably, excess OPCs are formed as a consequence of prolonged OPC production from neural precursor cells. We conclude that Nkx2.2 promotes timely specification and differentiation of myelinating oligodendrocyte lineage cells from species representing different vertebrate taxa.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping