PMID- 22051878
OWN - NLM
STAT- MEDLINE
DCOM- 20111223
LR  - 20220309
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 25
IP  - 22
DP  - 2011 Nov 15
TI  - Neuropilins are positive regulators of Hedgehog signal transduction.
PG  - 2333-46
LID - 10.1101/gad.173054.111 [doi]
AB  - The Hedgehog (Hh) pathway is essential for vertebrate embryogenesis, and 
      excessive Hh target gene activation can cause cancer in humans. Here we show that 
      Neuropilin 1 (Nrp1) and Nrp2, transmembrane proteins with roles in axon guidance 
      and vascular endothelial growth factor (VEGF) signaling, are important positive 
      regulators of Hh signal transduction. Nrps are expressed at times and locations 
      of active Hh signal transduction during mouse development. Using cell lines 
      lacking key Hh pathway components, we show that Nrps mediate Hh transduction 
      between activated Smoothened (Smo) protein and the negative regulator Suppressor 
      of Fused (SuFu). Nrp1 transcription is induced by Hh signaling, and Nrp1 
      overexpression increases maximal Hh target gene activation, indicating the 
      existence of a positive feedback circuit. The regulation of Hh signal 
      transduction by Nrps is conserved between mammals and bony fish, as we show that 
      morpholinos targeting the Nrp zebrafish ortholog nrp1a produce a specific and 
      highly penetrant Hh pathway loss-of-function phenotype. These findings enhance 
      our knowledge of Hh pathway regulation and provide evidence for a conserved nexus 
      between Nrps and this important developmental signaling system.
FAU - Hillman, R Tyler
AU  - Hillman RT
AD  - Department of Genetics, Stanford University School of Medicine, California 94305, 
      USA.
FAU - Feng, Brian Y
AU  - Feng BY
FAU - Ni, Jun
AU  - Ni J
FAU - Woo, Wei-Meng
AU  - Woo WM
FAU - Milenkovic, Ljiljana
AU  - Milenkovic L
FAU - Hayden Gephart, Melanie G
AU  - Hayden Gephart MG
FAU - Teruel, Mary N
AU  - Teruel MN
FAU - Oro, Anthony E
AU  - Oro AE
FAU - Chen, James K
AU  - Chen JK
FAU - Scott, Matthew P
AU  - Scott MP
LA  - eng
GR  - R01 ARO46786/PHS HHS/United States
GR  - T32 CA009302/CA/NCI NIH HHS/United States
GR  - F32CA134146/CA/NCI NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - F32 CA134146/CA/NCI NIH HHS/United States
GR  - R01 CA136574/CA/NCI NIH HHS/United States
GR  - R01 GM095948/GM/NIGMS NIH HHS/United States
GR  - R01 AR046786/AR/NIAMS NIH HHS/United States
GR  - R01GM095948/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111103
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Neuropilin-2)
RN  - 0 (Neuropilins)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Repressor Proteins)
RN  - 0 (Smo protein, mouse)
RN  - 0 (Smoothened Receptor)
RN  - 0 (Sufu protein, mouse)
RN  - 144713-63-3 (Neuropilin-1)
SB  - IM
EIN - Genes Dev. 2012 Mar 15;26(6):630
MH  - Animals
MH  - Feedback, Physiological
MH  - Gene Expression Regulation, Developmental
MH  - Hedgehog Proteins/*metabolism
MH  - Mice
MH  - Neuropilin-1/genetics/metabolism
MH  - Neuropilin-2/genetics/metabolism
MH  - Neuropilins/*metabolism
MH  - RNA Interference
MH  - Receptors, G-Protein-Coupled/metabolism
MH  - Repressor Proteins/metabolism
MH  - *Signal Transduction
MH  - Smoothened Receptor
PMC - PMC3222900
EDAT- 2011/11/05 06:00
MHDA- 2011/12/24 06:00
PMCR- 2011/11/15
CRDT- 2011/11/05 06:00
PHST- 2011/11/05 06:00 [entrez]
PHST- 2011/11/05 06:00 [pubmed]
PHST- 2011/12/24 06:00 [medline]
PHST- 2011/11/15 00:00 [pmc-release]
AID - gad.173054.111 [pii]
AID - 10.1101/gad.173054.111 [doi]
PST - ppublish
SO  - Genes Dev. 2011 Nov 15;25(22):2333-46. doi: 10.1101/gad.173054.111. Epub 2011 Nov 
      3.