Award details

Elucidating the interplay between cellular behaviour and tissue mechanics during morphogenesis

Reference	BB/F012845/1
Principal Investigator / Supervisor	Professor Alfonso Martinez Arias
Co-Investigators / Co-Supervisors	Dr Nicole Gorfinkiel
Institution	University of Cambridge
Department	Genetics
Funding type	Research
Value (£)	358,869
Status	Completed
Type	Research Grant
Start date	01/04/2008
End date	31/03/2011
Duration	36 months

Abstract

Half way through embryonic development, the epidermis of Drosophila exhibits a gap covered by a squamous epithelium, the amnioserosa. Dorsal closure (DC) is the process whereby interactions between the two epithelia establish epidermal continuity. This process is an excellent model system to study the cellular activities involved in morphogenesis, the set of complex and dynamic interactions between groups of cells that govern the formation of 3D structures, and to correlate them with biophysical properties of the cells. A number of studies suggest that the activities of the cytoskeleton and of the adhesion systems of a cell must be carefully regulated during morphogenesis. Here we propose to study the coordination of these two activities during DC combining classical genetics with biophysical measurements of cellular parameters. The resulting information will be integrated into a finite element model of the process which should inform about emergent properties at the tissue level. Specifically, using state of the art microscopy we shall probe the function of a-catenin that links the Cadherin based adhesion system with the cytoskeleton. In parallel, we shall use laser-ablation of cells and cell boundaries to analyze the dynamic distribution of forces during dorsal closure. This analysis will reveal the dynamic map of tensions that underlies the process and, through a genetic perturbation analysis, will allow us to relate molecular events at the single cell level with tissue behaviour. The data gathered from these analyses will be used to generate a computational simulation of dorsal closure, which will have predictive value, will yield new insights into the nature of morphogenesis through a constructive feedback on the experiments.

Summary

Cells are the building blocks for the tissues and organs that make up organisms. One strategy used by cells in this process is to arrange themselves in sheets, called epithelia, that are then folded into shapes through a kind of molecularly driven bio-oregamy. Epithelia are configured by cells joining each other through specialized attachments called 'junctions'. Cells contain a cellular scaffolding or cytoskeleton that is linked to the 'junctions' and allows them to change and maintain their shape in a controlled manner. Bending and folding these sheets makes organisms and failures in these activities result in deformations or structural defects. For these reasons, it is not surprising that the coordination of the activity of the cytoskeleton and that of the 'junctions' between cells is a crucial element in the folding of the sheets. Over the years, the fruit fly Drosophila has proven an excellent system to unravel the mechanics of animal development. Recently it is also proving a valuable research tool to analyze the activities of groups of cells and the movement and folding of epithelia. Here we plan to use the fly embryo to study the molecular basis of bending, folding and interactions between sheets of cells. We shall do this by combining classical biological techniques anchored in the study of the effects of mutations on a particular process with engineering type analysis of the forces generated by cells at the level of tissues.

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

I accept the terms and conditions of use (opens in new window)

export PDF file

back to list new search