Control mechanisms and robustness of multicellular symmetry breaking

Project Information

BREAKDANCE

Grant agreement ID: 101072123

DOI

10.3030/101072123

EC signature date 10 October 2023

Start date 1 January 2024

End date 31 December 2029

Funded under

• European Research Council (ERC)

Total cost

€ 10 259 926,00

EU contribution

€ 10 259 926,00

Coordinated by

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany

Periodic Reporting for period 1 - BREAKDANCE (Control mechanisms and robustness of multicellular symmetry breaking)

Reporting period: 2024-01-01 to 2025-06-30

Summary of the context and overall objectives of the project

How can tissue shapes and patterns emerge reproducibly and robustly in multicellular systems like animals?
The animal body plan is built via a multicellular choreography generally assumed to be under the direct control of specific genetic programs. According to this view, the fertilized egg organizes into complex patterns of differentiated cells through the action of gene regulatory networks and several studies in different organisms have revealed conserved roles of a small set of specific proteins. However, this view obscures the fact that embryonic geometry is defined by specific tissue boundaries that impose constraints to embryonic morphologies, including shape, dimensionality (2D, 3D), and size.
To reveal the fundamental mechanisms driving robust symmetry-breaking and axis formation, science face the challenge of integrating global geometry with biochemical and mechanical interactions, active cellular motions, and cell division and death.
The BREAKDANCE consortium has the apt complementary expertise - experimental, technical and theoretical - needed to promote a profound leap in our still incomplete understanding of how symmetry breaking and shape formation is controlled in embryogenesis. This will be achieved by bringing together a team of highly interdisciplinary researchers that can tackle a complex biological problem, combining methods and concepts from both physics and biology and integrating quantitative information across multiple scales.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In the first 18 months of the project, the BREAKDANCE consortium has focused its efforts on building a strong team of researchers and on developing tools and methods. The consortium has worked on establishing cell culture conditions, generation of aggregates and gastruloids, confinement and manipulation of the geometry. Also, relevant animal lines have been established. As the project is highly demanding in terms of imaging capacity, the consortium has set up several imaging platforms such as two-photon imaging, single-objective light sheet microscopy and a device for high-throughput imaging of 3D samples. Moreover, the consortium developed a variety of imaging analysis pipeline. In parallel, the consortium has cemented several biological assays and analysis.
First results of the project on metabolic control of spatial symmetry breaking and intracellular mechanical properties have been recently published.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The robustness of symmetry breaking across species of varying embryo shape and size is astonishing given the complexity of in vivo environments, prompting the question of whether there is a common underlying control mechanism. Within the scope of BREAKDANCE, the consortium has started to assemble the building blocks which will allow probing this question in a tractable manner in controlled in vitro systems. The work ahead should pave the way for a transformation of both experimental and conceptual approaches to study tissue development, and will thus also have a significant impact on the emerging fields of regenerative tissue biology and synthetic tissue design.