Cell and Tissue Dynamics Group

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Research

The development of multi-cellular organisms involves changes of tissue structure, where groups of cells differentiate, change shape and move to form new tissues or organs. While many genes and molecules involved in these and other biological processes have been identified, the mechanical basis of each sequence of cell shape changes remains elusive.


The aim of our group is to understand and eventually connect these sequence of events. We are interested in how life organisms shape themselves: from the cytoskeletal arrangement and deployment of molecular motors inside the cells, to the resulting cell-cell interactions that determine tissue shape and function.


Models of cytoskeletal contraction mechanisms


One major focus of our group is trying to understand the many mechanisms by which cytoskeletal networks contract and generate forces.

The best known mechanism of cytoskeletal contraction is the filament buckling, which relies on the combined actions of myosin motors and crosslinkers.

Cytoskeletal networks can also contract via other mechanism, such as the polarity sorting, which relies on the filament end-dwelling property of microtubule motors such as dynein and kinesin.

There are also less common mechanisms that can drive cytoskeletal contraction. In a recent collaboration with the LĂ©nart lab, we showed that networks can coherently contract in the presence of a crosslinker that harness the the free energy of disassembling actin filaments.


These 3 mechanism are only a subset of all the possible ways that cytoskeletal networks can contract. The image on the right show other theoretical mechanism of contraction and expansion of networks. The first column shows an illustration of the mechanism, the second column the involved connectors, and the third column shows their combinations into distinct mechanical configurations.


Our group is interested in exploring these different mechanism under different biological contexts and how they contribute to force generation and transmission within tissues, both at homeostasis and during development.



Contact us if you are a student interested in working on this topic.

Models of tissue morphogenesis


Another area of activity in the group is the modelling of developmental processes at the cell and tissue scales. Our aim is to find out which set of cell behaviors and external constraints are necessary and sufficient to reproduce the wide variety of patterned structures in animal anatomy.

Segmentation according to the Clock and Wavefront model


Many structures of our bodies, such as our vertebrae, ribs and skeletal muscles, arise from and are preceded from transient structures called somites.


This process (somitogenesis) happens as our bodies are elongating and each somite is created at regular temporal and spatial sequence from a growing and undifferentiated tissue called PSM (pre-somitic mesoderm).


The clock and wevefront model postualtes that the interaction of a moving wavefront at the tissue level and an oscillating molecular clock, at the cellular level, is sufficient to determine the placement of the boundaries between the somites (figure on the left).


The video on the left shows a multi-scale simulation where we modeled the cell adhesion properties (left panel), the wavefront as a diffusible fgf8 gradient (central panel), and the clock as a set of equations describing the interactions of the FGF, WNT and Delta-Notch pathways (right panel, showing only the level of Lfng on each cell).

Segmentation as a self-organized process

In a notable work by Claudio Stern and colleagues, quail somites were induced to form simultaneously, without the presence of any internal molecular clock or external wavefront.

To further support their finding, we showed through simulations that cells undergoing mesenchymal-to-epitheial transition (polarization + elongation + apical constriction) can form somite-like structures autonomously.

Other lines of research on the topic of developmental biology include computer simulations of:

  •   Limb-bud formation
  •   Gut morphogenesis,
  •   Epithelial patterning,
  •   Brain morphogenesis.

There are open positions for students interested in working on these topics. Please, contact us!

Our research is not limited to these two categories. Occasionally we also adventure over other related areas:

 - Cell migration

 - Dermal maturation

 - Kidney disease

 - Foam dynamics

 - Cell sorting


Check our publications' page for a full list of papers.