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In vivo characterization of novel actin dynamic regulators during cell migration

Objective

Cell migration is a critical process for embryogenesis, immune cell function and wound healing as well as cancer progression. Most normal cells migrate by protruding the plasma membrane forward through actin polymerization. The formation of a protrusion requires activation of the small GTPase Rac1 that in turn activates the WAVE complex, which induces branched actin networks through the Arp2/3 complex. For efficient cell migration, membrane protrusion at the leading edge must be sustained. Conversely, cells need to retract membrane protrusion to stop cell migration or turn. The tight control of protrusion lifetime and directional persistence is thus critical to fine tune cell migration. At the molecular level, persistence is controlled by positive and negative feedback loops. However, only few of these feedback loops have been identified and almost none has been characterized, in particular in vivo. In a joint effort with two other labs, proteomic screens were used to identify proteins that interact with the WAVE complex and whose interaction is modulated by branched actin. Based on different selection criteria such as their role in actin dynamics in vitro, conservation in fish, and absence of in vivo data, I selected three candidates. I will unravel their in vivo function at different scales, from embryonic development, to cell migration, to membrane protrusion and cytoskeleton dynamics. Actin feedback loops regulating cell migration will be specifically dissected. To do so, I will take advantage of two complementary and well characterized cellular models: endodermal cells and prechordal plate cells. Endodermal cells perform a random walk, while prechordal plate cells exhibit a directed collective migration. This project, which relies on validated unbiased screens and well established cellular models and approaches, will provide new insights in our understanding of actin dynamics regulation and mechanisms that fine tune cell migration.
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Coordinator

ECOLE POLYTECHNIQUE

Address

Route De Saclay
91128 Palaiseau Cedex

France

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 295 061,76

Project information

Grant agreement ID: 840201

Status

Grant agreement signed

  • Start date

    1 June 2020

  • End date

    31 May 2023

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 295 061,76

  • EU contribution

    € 295 061,76

Coordinated by:

ECOLE POLYTECHNIQUE

France