PT  - JOURNAL ARTICLE
AU  - Suhyun Kim
AU  - Jun-Dae Kim
AU  - Ah-Young Chung
AU  - Hyung-Seok Kim
AU  - Young-Seop Kim
AU  - Myoung-Jin Kim
AU  - Soonil Koun
AU  - You Mie Lee
AU  - Myungchull Rhee
AU  - Hae-Chul Park
AU  - Tae-Lin Huh
TI  - Antagonistic Regulation of PAF1C and p-TEFb Is Required for Oligodendrocyte Differentiation
AID  - 10.1523/JNEUROSCI.5344-11.2012
DP  - 2012 Jun 13
TA  - The Journal of Neuroscience
PG  - 8201--8207
VI  - 32
IP  - 24
4099  - http://www.jneurosci.org/content/32/24/8201.short
4100  - http://www.jneurosci.org/content/32/24/8201.full
SO  - J. Neurosci.2012 Jun 13; 32
AB  - Oligodendrocytes are myelinating glial cells in the CNS and are essential for proper neuronal function. During development, oligodendrocyte progenitor cells (OPCs) are specified from the motor neuron precursor domain of the ventral spinal cord and differentiate into myelinating oligodendrocytes after migration to the white matter of the neural tube. Cell cycle control of OPCs influences the balance between immature OPCs and myelinating oligodendrocytes, but the precise mechanism regulating the differentiation of OPCs into myelinating oligodendrocytes is unclear. To understand the mechanisms underlying oligodendrocyte differentiation, an N-ethyl-N-nitrosourea-based mutagenesis screen was performed and a zebrafish leo1 mutant, dalmuri (dalknu6) was identified in the current study. Leo1 is a component of the evolutionarily conserved RNA polymerase II-associated factor 1 complex (PAF1C), which is a positive regulator of transcription elongation. The dalknu6 mutant embryos specified motor neurons and OPCs normally, and at the appropriate time, but OPCs subsequently failed to differentiate into myelinating oligodendrocytes and were eliminated by apoptosis. A loss-of-function study of cdc73, another member of PAF1C, showed the same phenotype in the CNS, indicating that PAF1C function is required for oligodendrocyte differentiation. Interestingly, inhibition of positive transcription elongation factor b (p-TEFb), rescued downregulated gene expression and impaired oligodendrocyte differentiation in the dalknu6 mutant and Cdc73-deficient embryos. Together, these results indicate that antagonistic regulation of gene expression by PAF1C and p-TEFb plays a crucial role in oligodendrocyte development in the CNS.