PMID- 28560839
OWN - NLM
STAT- MEDLINE
DCOM- 20180727
LR  - 20180815
IS  - 1097-0177 (Electronic)
IS  - 1058-8388 (Linking)
VI  - 247
IP  - 1
DP  - 2018 Jan
TI  - Suppressor of fused controls cerebellar neuronal differentiation in a manner 
      modulated by GLI3 repressor and Fgf15.
PG  - 156-169
LID - 10.1002/dvdy.24526 [doi]
AB  - BACKGROUND: Deficiency of Suppressor of Fused (SuFu), an intracellular mediator 
      of Hedgehog signaling, in the murine mid-hindbrain disrupts cerebellar 
      morphogenesis and cell differentiation in a manner that is rescued by 
      constitutive expression of GLI3 transcriptional repressor (GLI3R). Here, we 
      determined SuFu functions in cerebellar radial precursors following the stage of 
      mid-hindbrain specification using a Blbp-Cre transgene. RESULTS: SuFu-deficient 
      cerebella were severely dysplastic, and characterized by laminar disorganization, 
      and delayed differentiation of ventricular zone-derived precursors. In vitro 
      analysis of cerebellar precursors isolated from control and mutant mice 
      demonstrated an increased proportion of radial glial precursors vs. Tuj1-positive 
      neurons in mutant cultures. Abnormal cell differentiation in SuFu-deficient 
      precursors was rescued by a constitutively expressed GLI3R knock-in allele, 
      albeit with variable penetrance. Using RNA expression analysis in control and 
      SuFu-deficient cerebellar anlage, we identified up-regulation of Fgf15 in mutant 
      tissue. Strikingly, exogenous hFGF19, a mFGF15 ortholog, inhibited neuronal 
      differentiation in cultures of wild-type cerebellar precursors. Moreover, 
      siRNA-mediated knockdown of Fgf15 in SuFu-deficient cerebellar precursors rescued 
      their delayed differentiation to neurons. CONCLUSIONS: Together, our results show 
      that SuFu promotes cerebellar radial precursor differentiation to neurons. SuFu 
      function is mediated in part by GLI3R and down-regulation of Fgf15 expression. 
      Developmental Dynamics 247:156-169, 2018. (c) 2017 Wiley Periodicals, Inc.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Kim, Jinny J
AU  - Kim JJ
AD  - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 
      Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada.
AD  - Department of Physiology, University of Toronto, Medical Sciences Building, 
      Toronto, ON, Canada.
FAU - Jiwani, Tayyaba
AU  - Jiwani T
AD  - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 
      Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada.
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Medical Sciences Building, Toronto, ON, Canada.
FAU - Erwood, Steven
AU  - Erwood S
AD  - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 
      Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada.
FAU - Loree, Jillian
AU  - Loree J
AD  - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 
      Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada.
FAU - Rosenblum, Norman D
AU  - Rosenblum ND
AUID- ORCID: 0000-0003-1767-6464
AD  - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 
      Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada.
AD  - Department of Physiology, University of Toronto, Medical Sciences Building, 
      Toronto, ON, Canada.
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Medical Sciences Building, Toronto, ON, Canada.
AD  - Division of Nephrology, The Hospital for Sick Children, Peter Gilgan Centre for 
      Research and Learning, Toronto, ON, Canada.
AD  - Department of Paediatrics, University of Toronto, Medical Sciences Building, 
      Toronto, ON, Canada.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170615
PL  - United States
TA  - Dev Dyn
JT  - Developmental dynamics : an official publication of the American Association of 
      Anatomists
JID - 9201927
RN  - 0 (Gli3 protein, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Repressor Proteins)
RN  - 0 (Sufu protein, mouse)
RN  - 0 (Zinc Finger Protein Gli3)
RN  - 0 (fibroblast growth factor 15, mouse)
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/*physiology
MH  - Cerebellum/cytology/*metabolism
MH  - Down-Regulation
MH  - Ependymoglial Cells/cytology/metabolism
MH  - Fibroblast Growth Factors/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neurogenesis/physiology
MH  - Neurons/cytology/*metabolism
MH  - RNA, Small Interfering
MH  - Repressor Proteins/*metabolism
MH  - Signal Transduction/physiology
MH  - Zinc Finger Protein Gli3/*metabolism
OTO - NOTNLM
OT  - SUFU-GLI regulation
OT  - cerebellar neurogenesis
OT  - radial glial differentiation
OT  - sonic hedgehog signaling
EDAT- 2017/06/01 06:00
MHDA- 2018/07/28 06:00
CRDT- 2017/06/01 06:00
PHST- 2017/02/02 00:00 [received]
PHST- 2017/04/25 00:00 [revised]
PHST- 2017/05/15 00:00 [accepted]
PHST- 2017/06/01 06:00 [pubmed]
PHST- 2018/07/28 06:00 [medline]
PHST- 2017/06/01 06:00 [entrez]
AID - 10.1002/dvdy.24526 [doi]
PST - ppublish
SO  - Dev Dyn. 2018 Jan;247(1):156-169. doi: 10.1002/dvdy.24526. Epub 2017 Jun 15.