Wingless/Wnt signal transduction requires distinct initiation and amplification steps that both depend on Arrow/LRP

Shahana Baig-Lewis; Wynne Peterson-Nedry; Marcel Wehrli

doi:10.1016/j.ydbio.2007.03.005

Wingless/Wnt signal transduction requires distinct initiation and amplification steps that both depend on Arrow/LRP

Shahana Baig-Lewis
, Wynne Peterson-Nedry
, Marcel Wehrli

School of Dentistry

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

Members of the Wg/Wnt family provide key intercellular signals during embryonic development and in the maintenance of homeostatic processes, but critical aspects of their signal transduction pathways remain controversial. We have found that canonical Wg signaling in Drosophila involves distinct initiation and amplification steps, both of which require Arrow/LRP. Expressing a chimeric Frizzled2-Arrow protein in flies that lack endogenous Wg or Arrow showed that this construct functions as an activated Wg receptor but is deficient in signal amplification. In contrast, a chimeric Arrow protein containing the dimerization domain of Torso acted as a potent amplifier of Wg signaling but could not initiate Wg signaling on its own. The two chimeric proteins synergized, so that their co-expression largely reconstituted the signaling levels achieved by expressing Wg itself. The amplification function of Arrow/LRP appears to be particularly important for long-range signaling, and may reflect a general mechanism for potentiating signals in the shallow part of a morphogen gradient.

Original language	English (US)
Pages (from-to)	94-111
Number of pages	18
Journal	Developmental Biology
Volume	306
Issue number	1
DOIs	https://doi.org/10.1016/j.ydbio.2007.03.005
State	Published - Jun 1 2007

Funding

We are grateful to Drs. Gary Ciment, Hugo Bellen, Ian Duncan, Barry Dickson, Naz Erdeniz, Sarah Smolik, Philip Copenhaver, Tracy Swanson and Steve DiNardo for providing critical reagents for this work. We also acknowledge the Bloomington Stock Center and the Developmental Studies Hybridoma Bank (DSHB) for providing us with fly stocks and antibodies, respectively. We thank Drs. Jan Christian, Philip Copenhaver, Steve DiNardo, Naz Erdeniz, Brian Johnstone, Richard Maurer and Mike Forte for comments on the manuscript and Rachel Dresbeck for editing the manuscript. We would also like to thank Drs. Stephanie Kaech Petri, Bruce Schnapp and John Williams for helping with fluorescence imaging. Jocelyn Early provided excellent technical assistance. This work was started in the laboratory of Steve DiNardo and initially supported by grant GM045747; the confocal microscope used in this study is part of the Metal Ion Core Facility, supported by P01-GM067166. This work was supported by NIH grant GM67029 to M.W.

Funders	Funder number
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health
National Institute of General Medical Sciences	R01GM067029

Keywords

Arrow
Axin
Frizzled
LRP
Morphogen gradient
Signal amplification
Wingless
Wnt signaling

ASJC Scopus subject areas

Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.ydbio.2007.03.005

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title = "Wingless/Wnt signal transduction requires distinct initiation and amplification steps that both depend on Arrow/LRP",

abstract = "Members of the Wg/Wnt family provide key intercellular signals during embryonic development and in the maintenance of homeostatic processes, but critical aspects of their signal transduction pathways remain controversial. We have found that canonical Wg signaling in Drosophila involves distinct initiation and amplification steps, both of which require Arrow/LRP. Expressing a chimeric Frizzled2-Arrow protein in flies that lack endogenous Wg or Arrow showed that this construct functions as an activated Wg receptor but is deficient in signal amplification. In contrast, a chimeric Arrow protein containing the dimerization domain of Torso acted as a potent amplifier of Wg signaling but could not initiate Wg signaling on its own. The two chimeric proteins synergized, so that their co-expression largely reconstituted the signaling levels achieved by expressing Wg itself. The amplification function of Arrow/LRP appears to be particularly important for long-range signaling, and may reflect a general mechanism for potentiating signals in the shallow part of a morphogen gradient.",

keywords = "Arrow, Axin, Frizzled, LRP, Morphogen gradient, Signal amplification, Wingless, Wnt signaling",

author = "Shahana Baig-Lewis and Wynne Peterson-Nedry and Marcel Wehrli",

note = "Funding Information: We are grateful to Drs. Gary Ciment, Hugo Bellen, Ian Duncan, Barry Dickson, Naz Erdeniz, Sarah Smolik, Philip Copenhaver, Tracy Swanson and Steve DiNardo for providing critical reagents for this work. We also acknowledge the Bloomington Stock Center and the Developmental Studies Hybridoma Bank (DSHB) for providing us with fly stocks and antibodies, respectively. We thank Drs. Jan Christian, Philip Copenhaver, Steve DiNardo, Naz Erdeniz, Brian Johnstone, Richard Maurer and Mike Forte for comments on the manuscript and Rachel Dresbeck for editing the manuscript. We would also like to thank Drs. Stephanie Kaech Petri, Bruce Schnapp and John Williams for helping with fluorescence imaging. Jocelyn Early provided excellent technical assistance. This work was started in the laboratory of Steve DiNardo and initially supported by grant GM045747; the confocal microscope used in this study is part of the Metal Ion Core Facility, supported by P01-GM067166. This work was supported by NIH grant GM67029 to M.W. ",

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doi = "10.1016/j.ydbio.2007.03.005",

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T1 - Wingless/Wnt signal transduction requires distinct initiation and amplification steps that both depend on Arrow/LRP

AU - Baig-Lewis, Shahana

AU - Peterson-Nedry, Wynne

AU - Wehrli, Marcel

N1 - Funding Information: We are grateful to Drs. Gary Ciment, Hugo Bellen, Ian Duncan, Barry Dickson, Naz Erdeniz, Sarah Smolik, Philip Copenhaver, Tracy Swanson and Steve DiNardo for providing critical reagents for this work. We also acknowledge the Bloomington Stock Center and the Developmental Studies Hybridoma Bank (DSHB) for providing us with fly stocks and antibodies, respectively. We thank Drs. Jan Christian, Philip Copenhaver, Steve DiNardo, Naz Erdeniz, Brian Johnstone, Richard Maurer and Mike Forte for comments on the manuscript and Rachel Dresbeck for editing the manuscript. We would also like to thank Drs. Stephanie Kaech Petri, Bruce Schnapp and John Williams for helping with fluorescence imaging. Jocelyn Early provided excellent technical assistance. This work was started in the laboratory of Steve DiNardo and initially supported by grant GM045747; the confocal microscope used in this study is part of the Metal Ion Core Facility, supported by P01-GM067166. This work was supported by NIH grant GM67029 to M.W.

PY - 2007/6/1

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N2 - Members of the Wg/Wnt family provide key intercellular signals during embryonic development and in the maintenance of homeostatic processes, but critical aspects of their signal transduction pathways remain controversial. We have found that canonical Wg signaling in Drosophila involves distinct initiation and amplification steps, both of which require Arrow/LRP. Expressing a chimeric Frizzled2-Arrow protein in flies that lack endogenous Wg or Arrow showed that this construct functions as an activated Wg receptor but is deficient in signal amplification. In contrast, a chimeric Arrow protein containing the dimerization domain of Torso acted as a potent amplifier of Wg signaling but could not initiate Wg signaling on its own. The two chimeric proteins synergized, so that their co-expression largely reconstituted the signaling levels achieved by expressing Wg itself. The amplification function of Arrow/LRP appears to be particularly important for long-range signaling, and may reflect a general mechanism for potentiating signals in the shallow part of a morphogen gradient.

AB - Members of the Wg/Wnt family provide key intercellular signals during embryonic development and in the maintenance of homeostatic processes, but critical aspects of their signal transduction pathways remain controversial. We have found that canonical Wg signaling in Drosophila involves distinct initiation and amplification steps, both of which require Arrow/LRP. Expressing a chimeric Frizzled2-Arrow protein in flies that lack endogenous Wg or Arrow showed that this construct functions as an activated Wg receptor but is deficient in signal amplification. In contrast, a chimeric Arrow protein containing the dimerization domain of Torso acted as a potent amplifier of Wg signaling but could not initiate Wg signaling on its own. The two chimeric proteins synergized, so that their co-expression largely reconstituted the signaling levels achieved by expressing Wg itself. The amplification function of Arrow/LRP appears to be particularly important for long-range signaling, and may reflect a general mechanism for potentiating signals in the shallow part of a morphogen gradient.

KW - Arrow

KW - Axin

KW - Frizzled

KW - LRP

KW - Morphogen gradient

KW - Signal amplification

KW - Wingless

KW - Wnt signaling

UR - https://www.scopus.com/pages/publications/34249296303

UR - https://www.scopus.com/pages/publications/34249296303#tab=citedBy

U2 - 10.1016/j.ydbio.2007.03.005

DO - 10.1016/j.ydbio.2007.03.005

M3 - Article

C2 - 17433287

AN - SCOPUS:34249296303

SN - 0012-1606

VL - 306

SP - 94

EP - 111

JO - Developmental Biology

JF - Developmental Biology

IS - 1

ER -

Wingless/Wnt signal transduction requires distinct initiation and amplification steps that both depend on Arrow/LRP

Abstract

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Keywords

ASJC Scopus subject areas

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