PMID- 19285058
OWN - NLM
STAT- MEDLINE
DCOM- 20090604
LR  - 20190603
IS  - 1095-564X (Electronic)
IS  - 0012-1606 (Linking)
VI  - 329
IP  - 2
DP  - 2009 May 15
TI  - Tow (Target of Wingless), a novel repressor of the Hedgehog pathway in 
      Drosophila.
PG  - 280-93
LID - 10.1016/j.ydbio.2009.02.037 [doi]
AB  - Hedgehog (Hh) signalling plays a crucial role in the development and patterning 
      of many tissues in both vertebrates and invertebrates. Aberrations in this 
      pathway lead to severe developmental defects and cancer. Hh signal transduction 
      in receiving cells is a well studied phenomenon; however questions still remain 
      concerning the mechanism of repression of the pathway activator Smoothened (Smo) 
      in the absence of Hh. Here we describe a novel repressor of the Hh pathway, 
      Target of Wingless (Tow). Tow represents the Drosophila homolog of a conserved 
      uncharacterised protein family. We show that Tow acts in Hh receiving cells, 
      where its overexpression represses all levels of Hh signalling, and that this 
      repression occurs upstream or at the level of Smo and downstream of the Hh 
      receptor Patched (Ptc). In addition, we find that like Ptc, overexpression of Tow 
      causes an accumulation of lipophorin in the wing disc. We demonstrate that loss 
      of tow enhances different ptc alleles in a similar manner to another pathway 
      repressor, Suppressor of Fused (SuFu), possibly through mediating Ptc dependant 
      lipophorin internalisation. Combined, these results demonstrate that Tow is an 
      important novel regulator of the Hh pathway in the wing imaginal disc, and may 
      shed light on the mechanism of Ptc repression of Smo.
FAU - Ayers, Katie L
AU  - Ayers KL
AD  - Institute of Developmental Biology and Cancer Research, CNRS UMR 6543, Centre de 
      Biochimie, Universite de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, 
      France.
FAU - Rodriguez, Ralph
AU  - Rodriguez R
FAU - Gallet, Armel
AU  - Gallet A
FAU - Ruel, Laurent
AU  - Ruel L
FAU - Therond, Pascal
AU  - Therond P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090310
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (DNA Primers)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Smoothened Receptor)
RN  - 0 (Tow protein, Drosophila)
RN  - 0 (ptc protein, Drosophila)
RN  - 0 (smo protein, Drosophila)
RN  - 149291-21-4 (hh protein, Drosophila)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Base Sequence
MH  - DNA Primers
MH  - Drosophila
MH  - Drosophila Proteins/*antagonists & inhibitors/chemistry/genetics/*physiology
MH  - Hedgehog Proteins/*antagonists & inhibitors/genetics
MH  - In Situ Hybridization
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/chemistry/*physiology
MH  - Receptors, Cell Surface/physiology
MH  - Receptors, G-Protein-Coupled/physiology
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction
MH  - Smoothened Receptor
EDAT- 2009/03/17 09:00
MHDA- 2009/06/06 09:00
CRDT- 2009/03/17 09:00
PHST- 2008/10/09 00:00 [received]
PHST- 2009/02/13 00:00 [revised]
PHST- 2009/02/28 00:00 [accepted]
PHST- 2009/03/17 09:00 [entrez]
PHST- 2009/03/17 09:00 [pubmed]
PHST- 2009/06/06 09:00 [medline]
AID - S0012-1606(09)00167-5 [pii]
AID - 10.1016/j.ydbio.2009.02.037 [doi]
PST - ppublish
SO  - Dev Biol. 2009 May 15;329(2):280-93. doi: 10.1016/j.ydbio.2009.02.037. Epub 2009 
      Mar 10.