Collective polarization model for gradient sensing via Dachsous-Fat intercellular signaling

Madhav Mani, Sidhartha Goyal, Kenneth D. Irvine, Boris I. Shraiman

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Dachsous-Fat signaling via the Hippo pathway influences proliferation during Drosophila development, and some of its mammalian homologs are tumor suppressors, highlighting its role as a universal growth regulator. The Fat/Hippo pathway responds to morphogen gradients and influences the in-plane polarization of cells and orientation of divisions, linking growth with tissue patterning. Remarkably, the Fat pathway transduces a growth signal through the polarization of transmembrane complexes that responds to both morphogen level and gradient. Dissection of these complex phenotypes requires a quantitative model that provides a systematic characterization of the pathway. In the absence of detailed knowledge of molecular interactions, we take a phenomenological approach that considers a broad class of simple models, which are sufficiently constrained by observations to enable insight into possible mechanisms. We predict two modes of local/cooperative interactions among Fat- Dachsous complexes, which are necessary for the collective polarization of tissues and enhanced sensitivity to weak gradients. Collective polarization convolves level and gradient of input signals, reproducing known phenotypes while generating falsifiable predictions. Our construction of a simplified signal transduction map allows a generalization of the positional value model and emphasizes the important role intercellular interactions play in growth and patterning of tissues.

Original languageEnglish (US)
Pages (from-to)20420-20425
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number51
DOIs
StatePublished - Dec 17 2013

Fingerprint

fats
gradients
phenotype
polarization
Drosophila
suppressors
dissection
regulators
molecular interactions
division
tumors
interactions
sensitivity
predictions
cells

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Cell-cell signaling
  • Modelling
  • Morphogenesis

Cite this

@article{5e6a25711193476d8245f5736cce14c6,
title = "Collective polarization model for gradient sensing via Dachsous-Fat intercellular signaling",
abstract = "Dachsous-Fat signaling via the Hippo pathway influences proliferation during Drosophila development, and some of its mammalian homologs are tumor suppressors, highlighting its role as a universal growth regulator. The Fat/Hippo pathway responds to morphogen gradients and influences the in-plane polarization of cells and orientation of divisions, linking growth with tissue patterning. Remarkably, the Fat pathway transduces a growth signal through the polarization of transmembrane complexes that responds to both morphogen level and gradient. Dissection of these complex phenotypes requires a quantitative model that provides a systematic characterization of the pathway. In the absence of detailed knowledge of molecular interactions, we take a phenomenological approach that considers a broad class of simple models, which are sufficiently constrained by observations to enable insight into possible mechanisms. We predict two modes of local/cooperative interactions among Fat- Dachsous complexes, which are necessary for the collective polarization of tissues and enhanced sensitivity to weak gradients. Collective polarization convolves level and gradient of input signals, reproducing known phenotypes while generating falsifiable predictions. Our construction of a simplified signal transduction map allows a generalization of the positional value model and emphasizes the important role intercellular interactions play in growth and patterning of tissues.",
keywords = "Cell-cell signaling, Modelling, Morphogenesis",
author = "Madhav Mani and Sidhartha Goyal and Irvine, {Kenneth D.} and Shraiman, {Boris I.}",
year = "2013",
month = "12",
day = "17",
doi = "10.1073/pnas.1307459110",
language = "English (US)",
volume = "110",
pages = "20420--20425",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "51",

}

Collective polarization model for gradient sensing via Dachsous-Fat intercellular signaling. / Mani, Madhav; Goyal, Sidhartha; Irvine, Kenneth D.; Shraiman, Boris I.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 51, 17.12.2013, p. 20420-20425.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Collective polarization model for gradient sensing via Dachsous-Fat intercellular signaling

AU - Mani, Madhav

AU - Goyal, Sidhartha

AU - Irvine, Kenneth D.

AU - Shraiman, Boris I.

PY - 2013/12/17

Y1 - 2013/12/17

N2 - Dachsous-Fat signaling via the Hippo pathway influences proliferation during Drosophila development, and some of its mammalian homologs are tumor suppressors, highlighting its role as a universal growth regulator. The Fat/Hippo pathway responds to morphogen gradients and influences the in-plane polarization of cells and orientation of divisions, linking growth with tissue patterning. Remarkably, the Fat pathway transduces a growth signal through the polarization of transmembrane complexes that responds to both morphogen level and gradient. Dissection of these complex phenotypes requires a quantitative model that provides a systematic characterization of the pathway. In the absence of detailed knowledge of molecular interactions, we take a phenomenological approach that considers a broad class of simple models, which are sufficiently constrained by observations to enable insight into possible mechanisms. We predict two modes of local/cooperative interactions among Fat- Dachsous complexes, which are necessary for the collective polarization of tissues and enhanced sensitivity to weak gradients. Collective polarization convolves level and gradient of input signals, reproducing known phenotypes while generating falsifiable predictions. Our construction of a simplified signal transduction map allows a generalization of the positional value model and emphasizes the important role intercellular interactions play in growth and patterning of tissues.

AB - Dachsous-Fat signaling via the Hippo pathway influences proliferation during Drosophila development, and some of its mammalian homologs are tumor suppressors, highlighting its role as a universal growth regulator. The Fat/Hippo pathway responds to morphogen gradients and influences the in-plane polarization of cells and orientation of divisions, linking growth with tissue patterning. Remarkably, the Fat pathway transduces a growth signal through the polarization of transmembrane complexes that responds to both morphogen level and gradient. Dissection of these complex phenotypes requires a quantitative model that provides a systematic characterization of the pathway. In the absence of detailed knowledge of molecular interactions, we take a phenomenological approach that considers a broad class of simple models, which are sufficiently constrained by observations to enable insight into possible mechanisms. We predict two modes of local/cooperative interactions among Fat- Dachsous complexes, which are necessary for the collective polarization of tissues and enhanced sensitivity to weak gradients. Collective polarization convolves level and gradient of input signals, reproducing known phenotypes while generating falsifiable predictions. Our construction of a simplified signal transduction map allows a generalization of the positional value model and emphasizes the important role intercellular interactions play in growth and patterning of tissues.

KW - Cell-cell signaling

KW - Modelling

KW - Morphogenesis

UR - http://www.scopus.com/inward/record.url?scp=84890832334&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890832334&partnerID=8YFLogxK

U2 - 10.1073/pnas.1307459110

DO - 10.1073/pnas.1307459110

M3 - Article

AN - SCOPUS:84890832334

VL - 110

SP - 20420

EP - 20425

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 51

ER -