PMID- 26272614
OWN - NLM
STAT- MEDLINE
DCOM- 20160106
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 290
IP  - 40
DP  - 2015 Oct 2
TI  - Microprocessor complex subunit DiGeorge syndrome critical region gene 8 (Dgcr8) 
      is required for schwann cell myelination and myelin maintenance.
PG  - 24294-307
LID - 10.1074/jbc.M115.636407 [doi]
AB  - We investigated the role of a key component of the Microprocessor complex, DGCR8, 
      in the regulation of myelin formation and maintenance. We found that 
      conditionally ablating Dgcr8 in Schwann cells (SCs) during development results in 
      an arrest of SC differentiation. Dgcr8 conditional knock-out (cKO) SCs fail to 
      form 1:1 relationships with axons or, having achieved this, fail to form myelin 
      sheaths. The expression of genes normally found in immature SCs, such as 
      sex-determining region Y-box 2 (Sox2), is increased in Dgcr8 cKO SCs, whereas the 
      expression of myelin-related genes, including the master regulatory transcription 
      factor early growth response 2 (Egr2), is decreased. Additionally, expression of 
      a novel gene expression program involving sonic hedgehog (Shh), activated de novo 
      in injured nerves, is elevated in Dgcr8 cKOs but not in Egr2 null mice, a model 
      of SC differentiation arrest, suggesting that the injury-related gene expression 
      program in Dgcr8 cKOs cannot be attributed to differentiation arrest. Inducible 
      ablation of Dgcr8 in adult SCs results in gene expression changes similar to 
      those found in cKOs, including an increase in the expression of Sox2 and Shh. 
      Analyses of these nerves mainly reveal normal myelin thickness and axon size 
      distribution but some dedifferentiated SCs and increased macrophage infiltration. 
      Together our data suggest that Dgcr8 is responsible for modulation of gene 
      expression programs underlying myelin formation and maintenance as well as 
      suppression of an injury-related gene expression program.
CI  - (c) 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Lin, Hsin-Pin
AU  - Lin HP
AD  - From the Department of Neurology and Center for Genetic Medicine, Northwestern 
      University Feinberg School of Medicine, Chicago, Illinois 60611 and.
FAU - Oksuz, Idil
AU  - Oksuz I
AD  - From the Department of Neurology and Center for Genetic Medicine, Northwestern 
      University Feinberg School of Medicine, Chicago, Illinois 60611 and.
FAU - Hurley, Edward
AU  - Hurley E
AD  - Hunter James Kelly Research Institute, University at Buffalo, State University of 
      New York, Buffalo, New York 14203.
FAU - Wrabetz, Lawrence
AU  - Wrabetz L
AD  - Hunter James Kelly Research Institute, University at Buffalo, State University of 
      New York, Buffalo, New York 14203.
FAU - Awatramani, Rajeshwar
AU  - Awatramani R
AD  - From the Department of Neurology and Center for Genetic Medicine, Northwestern 
      University Feinberg School of Medicine, Chicago, Illinois 60611 and 
      r-awatramani@northwestern.edu.
LA  - eng
GR  - P30 CA060553/CA/NCI NIH HHS/United States
GR  - R01 NS071081/NS/NINDS NIH HHS/United States
GR  - 1R01NS071081-01/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150813
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Dgcr8 protein, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA-Binding Proteins)
RN  - EC 3.1.26.3 (Dicer1 protein, mouse)
RN  - EC 3.1.26.3 (Ribonuclease III)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
MH  - Animals
MH  - Axons/metabolism
MH  - Cell Differentiation
MH  - Crosses, Genetic
MH  - DEAD-box RNA Helicases/metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - MicroRNAs/metabolism
MH  - Myelin Sheath/*metabolism
MH  - Phenotype
MH  - RNA-Binding Proteins/*metabolism
MH  - Ribonuclease III/metabolism
MH  - Schwann Cells/*metabolism
PMC - PMC4591815
OTO - NOTNLM
OT  - Schwann cells
OT  - cell differentiation
OT  - conditional knockouts
OT  - development
OT  - gene expression
OT  - gene regulation
OT  - microRNA (miRNA)
OT  - mouse genetics
OT  - myelin
OT  - peripheral nervous system
EDAT- 2015/08/15 06:00
MHDA- 2016/01/07 06:00
PMCR- 2016/10/02
CRDT- 2015/08/15 06:00
PHST- 2015/01/06 00:00 [received]
PHST- 2015/08/15 06:00 [entrez]
PHST- 2015/08/15 06:00 [pubmed]
PHST- 2016/01/07 06:00 [medline]
PHST- 2016/10/02 00:00 [pmc-release]
AID - S0021-9258(20)44662-9 [pii]
AID - M115.636407 [pii]
AID - 10.1074/jbc.M115.636407 [doi]
PST - ppublish
SO  - J Biol Chem. 2015 Oct 2;290(40):24294-307. doi: 10.1074/jbc.M115.636407. Epub 
      2015 Aug 13.