Guiding massive collective migration, and fusion, of Drosophila epithelial cells – GuideFusion

GuideFusion is based on an integrative approach including advanced cellular imaging, developmental biology, biophysics and theory. We have formed a new consortium composed of a biophysicist with recognized expertise in imaginary disc mechanics (P#1, Loïc Le Goff), a drosophila geneticist specialized in gene structuring and cytoskeleton regulation (P#2, François Payre) and two theoretical physicists with expertise in modeling collective migration, tissue mechanics and genetic patterning (P#3, Vincent Hakim and Francis Corson).

The results obtained, one year after the start of the project, concern the development of imaging methods as well as the study of the biological process.

We have developed a scanning fluorescence microscope, which dynamically adapts its scanning pattern to the imaging of epithelial surfaces through an algorithmic search of informative pixels. The technique allows to reduce the light irradiation of the sample by a factor of 100x without deteriorating the quality of the images when observing curved and sparsely labeled structures, such as the adherent junctions of the imaginal wing disc (the object of study of GuideFusion).

The biological results obtained show that :
1-The migration results from a combination of the contraction of the substrate (the larval epidermis) in the initial phase of migration and the migration of the discs on the substrate at long times.
2-The migration of the discs highlights the role of filamentous structures which help migration through their intrinsic tension.

These results open up several perspectives:
-From a technical point of view, the imaging method developed is likely to be of interest to a large community of researchers interested in the imaging of biological tissues, especially when their object of study is sensitive to light. The optimization of the illumination path of samples is also likely to help the development of new rapid imaging methods.
-From a fundamental point of view, our observations show the importance of the role of the substrate in collective migration mechanisms.

1.Ben Amar M, Nassoy P., LeGoff L. (2019) Physics of growing biological tissues: The complex cross talk between cell activity, growth and resistance. Philosophical Transactions of the Royal Society A. DOI: 10.1098/rsta.2018.0070

2.Abouakil F., Galland F., LeGoff L. An adaptive scanning strategy for the imaging of biological surfaces (preprint).

Animal development critically relies on the migration of groups of cells, able to move over large distances and fuse with target tissues. How cell intrinsic factors and external cues are integrated to precisely guide collective migration of cells and their eventual fusion with their target is still poorly understood. The objective of GuideFusion is to decipher the feedback between patterning/positional information and migration that leads to the refined guidance of massive groups of cells, using Drosophila wings as a model system. We will address the following questions: How does positional information affect migration of cells? How is spatial information converted by the cytoskeleton into a mechanical actuation to move cells? What are the mechanisms by which cells coordinate their motion?

GuideFusion builds on an integrative approach including cutting-edge imaging, developmental biology, biophysics and theory from three groups with complimentary expertise.We formed a new consortium composed of a biophysicist with a recognized expertize in imaginal disc mechanics (P#1, Loïc Le Goff), a Drosophila geneticist specialist in gene patterning and the regulation of cytoskeleton (P#2, François Payre) and two theoretical physicists expert in the modeling of collective migration, tissue mechanics and patterning (P#3, Vincent Hakim and Francis Corson).

The main expected outcomes of the GuideFusion project are:
1-The characterization of the cytoskeletal dynamics that underlie tissue guidance in connection with gene patterning.
2-The investigation of the mechanics of migration, to address how the cytoskeletal activity at the front may lead to the mechanical actuation of this massive cluster of cells.
3-The iterative construction of a mathematical model of tissue guidance by a constant back and forth between theory and experiments.
4-The critical test of our understanding of the process by perturbative experiments.

The results of our project will be of direct relevance for a number of normal and pathological processes where collective cell migration is at play, in a broad range of fields including cell and developmental biology. Our results should also attract the interest of the biomedical community working on human malformations associated with altered fusion (vestibular system, neural tube, palate, heart, ...) which account for a large fraction of birth defects.