Nicholas H. Brown

University of Cambridge

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Co-Authors

Giulia Antonazzo

University of Cambridge

María D. Martín-Bermudo

Universidad Pablo de Olavide

Helen Attrill

University of Cambridge

Norbert Perrimon

Harvard University

Steven J Marygold

University of Cambridge

Jim Thurmond

Indiana University Bloomington

Gillian Millburn

University of Cambridge

Benjamin Klapholz

University of Cambridge

Victor Strelets

Indiana University Bloomington

Joshua L. Goodman

Indiana University Bloomington

Cooperative Institutions

Université de Montréal

224

Nationwide Children's Hospital

223

Centre Hospitalier Universitaire Sainte-Justine

223

Karolinska Institutet

222

University College London

151

SIB Swiss Institute of Bioinformatics

149

European Bioinformatics Institute

141

Stanford University

139

University of Cambridge

118

Phoenix Bioinformatics

111

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The integrin adhesion complex changes its composition and function during morphogenesis of an epithelium

Journal of Cell Science (2009)

Isabelle Delon Nicholas H. Brown

Cell adhesion to the extracellular matrix (ECM) is mediated by the integrin family of transmembrane receptors. Integrins link ECM ligands to the cytoskeleton, providing strong attachment to enable cell-shape change and tissue integrity. This connection is made possible by an intracellular complex of proteins, which links to actin filaments and controls signalling cascades that regulate cytoskeletal rearrangements. We have identified stress-fibre-associated focal adhesions that change their composition during tissue morphogenesis. Early expression of alphaPS1betaPS integrin decreases the levels of the actin-nucleating factors Enabled, Diaphanous and profilin, as well as downregulating the amount of F-actin incorporated into the stress fibres. As follicle cells mature in their developmental pathway and become squamous, the integrin in the focal adhesions changes from alphaPS1betaPS to alphaPS2betaPS. During the switch, stress fibres increase their length and change orientation, first changing by 90 degrees and then reorienting back. The normal rapid reorientation requires new expression of alphaPS2betaPS, which also permits recruitment of the adaptor protein tensin. Unexpectedly, it is the extracellular portion of the alphaPS2 subunit that provides the specificity for intracellular recruitment of tensin. Molecular variation of the integrin complex is thus a key component of developmentally programmed morphogenesis.

Tensin

10.1242/jcs.055996

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Citations (71)

Specific tracheal migration is mediated by complementary expression of cell surface proteins

Genes & Development (2001)

Muriel Boube María D. Martín-Bermudo Nicholas H. Brown Jordi Casanova

Migration of the Drosophila tracheal cells relies on cues provided by nearby cells; however, little is known about how these signals specify a migratory path. Here we investigate the role of cell surface proteins in the definition of such a pathway. We have found that the PS1 integrin is required in the tracheal cells of the visceral branch, whereas the PS2 integrin is required in the visceral mesoderm; both integrins are necessary for the spreading of the visceral branch over its substratum. This is the first identification of a cell surface molecule with expression restricted to a subset of tracheal cells that all migrate in a given direction. We have also found that expression of PS1 in the visceral branch is regulated by the genes that direct tracheal cell migration, showing that integrin expression is part of the cell-fate program that they specify. These results support a model in which signal transduction determines the tracheal migratory pathways by regulating the expression of cell surface proteins, which in turn interact with surface molecules on the surrounding cell population.

10.1101/gad.195501

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Citations (59)

Cell–Matrix Adhesion: The Wech Connection

Current Biology (2008)

Isabelle Delon Nicholas H. Brown

Matrix (chemical analysis)

10.1016/j.cub.2008.03.047

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Citations (3)

Anchors and Signals

Current topics in developmental biology/Current Topics in Developmental Biology (2015)

Aidan Maartens Nicholas H. Brown

Mechanotransduction

10.1016/bs.ctdb.2014.11.020

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Citations (45)

Talin – the master of integrin adhesions

Journal of Cell Science (2017)

Benjamin Klapholz Nicholas H. Brown

ABSTRACT Talin has emerged as the key cytoplasmic protein that mediates integrin adhesion to the extracellular matrix. In this Review, we draw on experiments performed in mammalian cells in culture and Drosophila to present evidence that talin is the most important component of integrin adhesion complexes. We describe how the properties of this adaptor protein enable it to orchestrate integrin adhesions. Talin forms the core of integrin adhesion complexes by linking integrins directly to actin, increasing the affinity of integrin for ligands (integrin activation) and recruiting numerous proteins. It regulates the strength of integrin adhesion, senses matrix rigidity, increases focal adhesion size in response to force and serves as a platform for the building of the adhesion structure. Finally, the mechano-sensitive structure of talin provides a paradigm for how proteins transduce mechanical signals to chemical signals.

CD49c

10.1242/jcs.190991

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Citations (274)

Spectraplakins

Current Biology (2014)

Sven Huelsmann Nicholas H. Brown

10.1016/j.cub.2014.02.003

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Citations (12)

Author response: Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila

eLife (2018)

Hannah J Green Annabel GM Griffiths Jari Ylänne Nicholas H. Brown

Myofibril

10.22025/camstag2.55988

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Integrin-dependent anchoring of a stem-cell niche

Nature Cell Biology (2007)

Guy Tanentzapf Danelle Devenport Dorothea Godt Nicholas H. Brown

10.1038/ncb1660

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Citations (209)

Identification of the Xenopus laevis cDNA for EXT1: A Phylogenetic Perspective

DNA sequence (2002)

April Hill Nicholas H. Brown Malcolm Hill Dan E. Wells

The EXT family of genes is involved in the developmentally important biosynthesis of heparan sulfate molecules. Members of the EXT family have a demonstrated role in gastrulation, wing formation in flies, and proper bone development in vertebrates. EXT family members have been isolated from several phylogenetically diverse species. We report here, the isolation of the first Xenopus laevis EXT1 family member and discuss the evolutionary origins of this gene family.

10.1080/10425170290029990

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An evidence-based model for representing signaling pathways in FlyBase

F1000Research (2019)

Giulia Antonazzo Helen Attrill Joshua L. Goodman Nicholas H. Brown

Open peer review

10.7490/f1000research.1116515.1

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