TY - JOUR
T1 - PIKE is essential for oligodendroglia development and CNS myelination
AU - Chan, Chi Bun
AU - Liu, Xia
AU - Zhao, Lixia
AU - Liu, Guanglu
AU - Lee, Chi Wai
AU - Feng, Yue
AU - Ye, Keiqang
N1 - Funding Information:
The authors thank Reed Otten for reading the manuscript. This work is supported by National Institutes of Health Grant R01NS045627 (to K.Y.) and Grant R01NS056097 (to Y.F.).
Publisher copyright:
Chan et al.
PY - 2014/2/4
Y1 - 2014/2/4
N2 - Oligodendrocyte (OL) differentiation and myelin development are complex events regulated by numerous signal transduction factors. Here, we report that phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor cells commit to differentiation. Conversely, depleting phosphoinositide- 3 kinase enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell differentiation. In both conventional PIKE knockout (PIKE-/-) and OL-specific PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE-/- OLs also display defects when forming myelin sheath on neuronal axons during neonatal development, which is partially rescued when PTEN is ablated. In addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE-/- mutant, leading to reduced expression of critical proteins for myelin development and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is delayed in PIKE-/- brain. Thus, PIKE plays pivotal roles to advance OL development and myelinogenesis through Akt/mTOR activation.
AB - Oligodendrocyte (OL) differentiation and myelin development are complex events regulated by numerous signal transduction factors. Here, we report that phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor cells commit to differentiation. Conversely, depleting phosphoinositide- 3 kinase enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell differentiation. In both conventional PIKE knockout (PIKE-/-) and OL-specific PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE-/- OLs also display defects when forming myelin sheath on neuronal axons during neonatal development, which is partially rescued when PTEN is ablated. In addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE-/- mutant, leading to reduced expression of critical proteins for myelin development and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is delayed in PIKE-/- brain. Thus, PIKE plays pivotal roles to advance OL development and myelinogenesis through Akt/mTOR activation.
UR - http://www.scopus.com/inward/record.url?scp=84893463527&partnerID=8YFLogxK
U2 - 10.1073/pnas.1318185111
DO - 10.1073/pnas.1318185111
M3 - Journal article
C2 - 24449917
AN - SCOPUS:84893463527
SN - 0027-8424
VL - 111
SP - 1993
EP - 1998
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
ER -
