We propose an interdisciplinary project,
at the interface of physics and developmental biology, to study the role of
mechanical and chemical signals in tissue patterning and emergence of shapes in
vertebrate embryos.
We are interested in understanding how
mechanical cues and possible feedbacks between mechanics and biochemical
pathways result in the formation of structures during the axial morphogenesis
of vertebrate embryos. We focus on the process of somite generation or
“somitogenesis”, which is a crucial tissue patterning event leading to the
formation of our musculoskeletal structures. Somites emerge as cells from the
posterior mesoderm differentiate under the action of morphogen gradients and
undergo mesenchymal to epithelial transition along the anterior-posterior axis,
form epithelial segments which detach periodically from one end. From a physics
point of view, the process is reminiscent to the pearling instability in soft
materials. Genetics has identified the biochemical pathways involved in cell
fate specification allowing to reproduce the early steps of segmentation in
vitro from explants or stem cells. However, the cross-talks between physics and
biology, leading to the morphogenetic step of somite generation with a
characteristic shape and size are not yet known.
Here, we will explore the role of tissue
mechanics and the impact of the micro-environment in which the tissue evolves
on the process of somitogenesis in chicken embryos.
We will develop experimental approaches
inspired by soft-matter physics and novel microfluidics techniques to:
i)
assess the role of mechanical cues and mechanosensitivity as the
mesoderm differentiates along the axis, in ex vivo controlled conditions, and
ii)
define the impact of the spatiotemporal morphogen gradients on
somite generation.
Later, we will integrate our findings with
the existing theoretical models to offer a comprehensive description of
somitogenesis combining physics and biology.