PMID- 33276084
OWN - NLM
STAT- MEDLINE
DCOM- 20211207
LR  - 20211214
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 148
DP  - 2021 Jan
TI  - Deletion of PDK1 in oligodendrocyte lineage cells causes white matter abnormality 
      and myelination defect in the central nervous system.
PG  - 105212
LID - S0969-9961(20)30487-3 [pii]
LID - 10.1016/j.nbd.2020.105212 [doi]
AB  - PDK1 (3-Phosphoinositide dependent protein kinase-1) is a member in the PI3K 
      (phosphatidylinositol 3 kinase) pathway and is implicated in neurodevelopmental 
      disease with microcephaly. Although the role of PDK1 in neurogenesis has been 
      broadly studied, it remains unknown how PDK1 may regulate oligogenesis in the 
      central nervous system (CNS). To address this question, we generated 
      oligodendrocyte (OL) lineage cells specific PDK1 conditional knockout (cKO) mice. 
      We find that PDK1 cKOs display abnormal white matter (WM), massive loss of mature 
      OLs and severe defect in myelination in the CNS. In contrast, these mutants 
      exhibit normal neuronal development and unchanged apoptosis in the CNS. We 
      demonstrate that deletion of PDK1 severely impairs OL differentiation. We show 
      that genetic or pharmacological inhibition of PDK1 causes deficit in the 
      mammalian target of rapamycin (mTor) signaling and down-regulation of Sox10. 
      Together, these results highlight a critical role of PDK1 in OL differentiation 
      during postnatal CNS development.
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Wang, He
AU  - Wang H
AD  - Department of Anesthesiology, Pain and Perioperative Medicine, The First 
      Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou 
      450052, China.
FAU - Liu, Mengjia
AU  - Liu M
AD  - State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model 
      Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 
      Xuefu Avenue, Nanjing, Jiangsu Province 210061, China.
FAU - Zou, Gang
AU  - Zou G
AD  - Department of Anesthesiology, The Second Affiliated Hospital, Nanjing Medical 
      University, 121 Jiangjiayuan Avenue, Nanjing, Jiangsu Province 210003, China.
FAU - Wang, Long
AU  - Wang L
AD  - State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model 
      Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 
      Xuefu Avenue, Nanjing, Jiangsu Province 210061, China.
FAU - Duan, Wenbin
AU  - Duan W
AD  - Department of General Surgery, The Second Clinical Medical College, Shenzhen 
      People's Hospital, Jinan University, Shenzhen 518000, China.
FAU - He, Xue
AU  - He X
AD  - Department of Anesthesiology, Pain and Perioperative Medicine, The First 
      Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou 
      450052, China.
FAU - Ji, Muhuo
AU  - Ji M
AD  - Department of Anesthesiology, Pain and Perioperative Medicine, The First 
      Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou 
      450052, China.
FAU - Zou, Xiaochuan
AU  - Zou X
AD  - State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model 
      Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 
      Xuefu Avenue, Nanjing, Jiangsu Province 210061, China.
FAU - Hu, Yimin
AU  - Hu Y
AD  - Department of General Surgery, The Second Clinical Medical College, Shenzhen 
      People's Hospital, Jinan University, Shenzhen 518000, China. Electronic address: 
      guyueym@njmu.edu.cn.
FAU - Yang, Jianjun
AU  - Yang J
AD  - Department of Anesthesiology, Pain and Perioperative Medicine, The First 
      Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou 
      450052, China. Electronic address: yjyangjj@126.com.
FAU - Chen, Guiquan
AU  - Chen G
AD  - State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model 
      Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 
      Xuefu Avenue, Nanjing, Jiangsu Province 210061, China. Electronic address: 
      chenguiquan@nju.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201201
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Pdk1 protein, mouse)
RN  - 0 (Pyruvate Dehydrogenase Acetyl-Transferring Kinase)
RN  - 0 (SOXE Transcription Factors)
RN  - 0 (Sox10 protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/*genetics
MH  - Cell Line
MH  - Cell Lineage
MH  - Down-Regulation
MH  - Mice
MH  - Mice, Knockout
MH  - Myelin Sheath/*metabolism
MH  - Oligodendrocyte Precursor Cells/*metabolism
MH  - Oligodendroglia/*metabolism
MH  - Pyruvate Dehydrogenase Acetyl-Transferring Kinase/antagonists & 
      inhibitors/*genetics
MH  - SOXE Transcription Factors/*genetics/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - White Matter/*metabolism
OTO - NOTNLM
OT  - Differentiation
OT  - Oligodendrocyte precursor cells
OT  - Oligodendrocytes
OT  - PDK1
OT  - White matter disease
EDAT- 2020/12/05 06:00
MHDA- 2021/12/15 06:00
CRDT- 2020/12/04 20:09
PHST- 2020/07/06 00:00 [received]
PHST- 2020/11/17 00:00 [revised]
PHST- 2020/11/29 00:00 [accepted]
PHST- 2020/12/05 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2020/12/04 20:09 [entrez]
AID - S0969-9961(20)30487-3 [pii]
AID - 10.1016/j.nbd.2020.105212 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2021 Jan;148:105212. doi: 10.1016/j.nbd.2020.105212. Epub 2020 Dec 
      1.