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Supracellular contractility dynamics and cell communication during collective chemotaxis.

Supracellular contractility dynamics and cell communication during collective chemotaxis.

Objective

Collective chemotaxis (CCT) is a fundamental process for embryonic development and cancer metastasis, where groups of cells collectively migrate in response to a chemoattractive signal. While single cell migration depends on polarised actomyosin mechanotransduction and signalling cascades within the same cell, in CCT these functions are shared between different cells to achieve a coordinated, ‘‘supracellular’’ translocation. The molecular mechanisms underlying coordination and cell-cell communication during CCT have been largely overlooked. I propose to address this issue using the neural crest (NC), a highly invasive mesenchymal cell population that migrates throughout the embryo via CCT. NC migration shows extensive similarities with cancer invasion, making it a useful model for studying metastatic migration. Preliminary experiments show that an actomyosin ring-shaped cable, which surrounds the NC cluster, contributes to maintain a supracellular organisation. Also, during CCT, gap junctions appear to regulate synchronous actomyosin contractions in cells located at the cluster’s rear. Therefore, I will study this contractility dynamics in-vitro and in-vivo using Xenopus and zebrafish. I will manipulate the actomyosin cable to understand its contribution to efficient chemotaxis. Then, I will investigate how gap junctions enable synchronisation between neighbouring cells, by imaging the spread of calcium waves in NC clusters and manipulating other diffusible messengers. This study will give significant insights into the mechanisms regulating CCT, which is crucial for deepening our understanding of morphogenesis and cancer biology.
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Coordinator

UNIVERSITY COLLEGE LONDON

Address

Gower Street
Wc1e 6bt London

United Kingdom

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 183 454,80

Project information

Grant agreement ID: 703100

Status

Grant agreement terminated

  • Start date

    1 October 2016

  • End date

    30 September 2018

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 183 454,80

  • EU contribution

    € 183 454,80

Coordinated by:

UNIVERSITY COLLEGE LONDON

United Kingdom