PMID- 21289193
OWN - NLM
STAT- MEDLINE
DCOM- 20110401
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 31
IP  - 5
DP  - 2011 Feb 2
TI  - Suppressor of fused controls mid-hindbrain patterning and cerebellar 
      morphogenesis via GLI3 repressor.
PG  - 1825-36
LID - 10.1523/JNEUROSCI.2166-10.2011 [doi]
AB  - Sonic Hedgehog and its GLI transcriptional effectors control foliation complexity 
      during cerebellar morphogenesis by promoting granule cell precursor 
      proliferation. Here, we reveal a novel contribution of Sonic Hedgehog-GLI 
      signaling to cerebellar patterning and cell differentiation by generating mice 
      with targeted deletion of Suppressor of Fused (SuFu), a regulator of Sonic 
      Hedgehog signaling, in the mid-hindbrain. Postnatal SuFu-deficient mice exhibit 
      impaired motor coordination and severe cerebellar mispatterning. SuFu conditional 
      knock-out embryos display abnormal mid-hindbrain morphology associated with 
      misexpression of Fgf8, and delayed differentiation and abnormal migration of 
      major cerebellar cell types. Sonic Hedgehog is ectopically expressed in the 
      external granule layer and Hedgehog signaling is upregulated. While expression of 
      full-length GLI transcriptional activators downstream of Hedgehogs is markedly 
      reduced, a processed form of GLI3, a transcriptional repressor, is essentially 
      lost. Genetic expression of a Gli3 allele encoding GLI3 repressor in 
      SuFu-deficient mice largely rescues abnormal cerebellar patterning and cell 
      differentiation observed in mice with SuFu deficiency alone. Together, our data 
      demonstrate that SuFu controls cerebellar patterning and cell differentiation in 
      a GLI3 repressor-dependent manner.
FAU - Kim, Jinny J
AU  - Kim JJ
AD  - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 
      Toronto, Ontario M5G 1X8, Canada.
FAU - Gill, Paul S
AU  - Gill PS
FAU - Rotin, Lianne
AU  - Rotin L
FAU - van Eede, Matthijs
AU  - van Eede M
FAU - Henkelman, R Mark
AU  - Henkelman RM
FAU - Hui, Chi-Chung
AU  - Hui CC
FAU - Rosenblum, Norman D
AU  - Rosenblum ND
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Fgf8 protein, mouse)
RN  - 0 (Gli3 protein, mouse)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Sufu protein, mouse)
RN  - 0 (Zinc Finger Protein Gli3)
RN  - 148997-75-5 (Fibroblast Growth Factor 8)
SB  - IM
MH  - Animals
MH  - Ataxia/genetics
MH  - Blotting, Western
MH  - *Cell Differentiation
MH  - *Cell Movement
MH  - Cells, Cultured
MH  - Cerebellum/cytology/growth & development
MH  - Fibroblast Growth Factor 8/genetics/metabolism
MH  - Gene Expression Regulation, Developmental
MH  - Hedgehog Proteins/deficiency/genetics/*metabolism
MH  - Immunohistochemistry
MH  - Kruppel-Like Transcription Factors/genetics/*metabolism
MH  - Magnetic Resonance Imaging
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Motor Activity/genetics
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Repressor Proteins/deficiency/genetics/*metabolism
MH  - Rhombencephalon/*cytology/*growth & development
MH  - Signal Transduction
MH  - Transcription, Genetic
MH  - Zinc Finger Protein Gli3
PMC - PMC6623745
EDAT- 2011/02/04 06:00
MHDA- 2011/04/02 06:00
PMCR- 2011/08/02
CRDT- 2011/02/04 06:00
PHST- 2011/02/04 06:00 [entrez]
PHST- 2011/02/04 06:00 [pubmed]
PHST- 2011/04/02 06:00 [medline]
PHST- 2011/08/02 00:00 [pmc-release]
AID - 31/5/1825 [pii]
AID - 3669378 [pii]
AID - 10.1523/JNEUROSCI.2166-10.2011 [doi]
PST - ppublish
SO  - J Neurosci. 2011 Feb 2;31(5):1825-36. doi: 10.1523/JNEUROSCI.2166-10.2011.