Martinez-Arias Lab
Department of Genetics, University of Cambridge
Research: Cell and tissue dynamics during morphogenesis
In the last twenty years we have learnt a great deal about the genes that mediate developmental events, the Gene Regulatory Networks which they configure and the consequences of disrupting these networks through mutation of individual elements. However, we know little about how these networks impinge on the way cells organize themselves in space and time to generate tissues and organs. Furthermore, we know very little about the higher order organization of cellular ensembles and their properties. These questions are within the realm of morphogenesis, or questions of form generation.
There are at least two reasons for this lack of knowledge. The first one is the emphasis on genes and mutations that has, rightfully, pervaded Biology for the last thirty years. The second one is the lack of proper methods to deal with the problems. The genetic analysis is being transcended by 'systems approaches' and these are generating methods, particularly imaging and image analysis methods, that allow the tackling of the questions posed by the organization and behaviour of cellular ensembles.
We are using the process of Dorsal Closure as an experimental system to explore morphogenesis. In particular, to analyze how individual cell activities and properties contribute to the large scale activity of a tissue.
This process leads to the closure of a gap (pink in picture) that
exists on the dorsal epidermis of the Drosophila embryo and which,
from the middle of embryogenesis is covered by a flat epithelium, the
amnioserosa, which is continuous with the epidermis. During Dorsal
Closure, the epidermis, in particular the dorsal epidermis (green in
Figure) expands and the amnioserosa contracts; in the end, the
epidermal gap is closed. This process requires careful spatial and
temporal control of the activity of the cytoskeleton and the cell
adhesion systems in both tissues and their coordination over time. For
this reason it provides a good system to study how molecular
activities at the level of single cells are transformed into large
scale activities at the level of tissues and how these tissues
coordinate their activities to generate a shape: the Drosophila
larva.
Our approach to this problem is to combine basic, classic Cell Biology with advanced imaging, particularly live imaging, to define observables and obtain measurements of several dynamic parameters of the cell. In parallel, and in collaboration with Richard Adams and Guy Blanchard (Department of PDN) we try to develop models that reflect the integration of the cell biological events into the activity and mechanics of the tissue involved.
Embryo at the beginning of dorsal closure (@10 hours after egg laying) with the dorsalmost epidermal cells highlighted by the expression of the Jun dependent phosphatase puckered (green).
The Tissue Morphogenesis Team
Sabine Schamberg - Postdoc
Pedro Machado - Postdoc
Ana Mateus - PhD student
Fan Cheng - PhD student
In collaboration with
Nicole Gorfinkiel (Centro Biologia Molecular, Madrid, Spain)
Jochen Guck (The Cavendish Laboratory, University of Cambridge)
Richard Adams (Department of Anatomy, University of Cambridge)
Guy Blanchard (Department of Anatomy, University of Cambridge)
Simon Guest (Department of Engineering, University of Cambridge)
Selected publications
Some of the publications upon which these studies are based:
Ring, J. and Martinez Arias, A. (1993)
puckered, a gene involved in position-specific cell differentiation in the dorsal epidermis of the Drosophila larva. Development.1993 Suppl. 251-259.
Martin Blanco, E., Gampel, A., Ring, J., Virdee, K. and Martinez Arias, A. (1998)
The puckered gene encodes a phosphatase that regulates JNK activity during dorsal closure in Drosophila. Genes and Dev. 12, 557-570.
Martin Blanco, E., Jarvis, B. and Martinez Arias, A. (1998)
Techniques update: crossreactivity of anti-dual-phosphorylated antibodies with actin. Trends in Cell Biology 8, 419.
Zecchini, V. Brennan, K. and Martinez Arias, A. (1999)
An activity of Notch regulates JNK signalling and affects dorsal closure in Drosophila. Current Biology 9, 460-469.
Jacinto, A., Wood, W., Balayo, T., Turmaine, M. Martinez Arias, A*. and Martin, P*. (2000)
Dynamic actin-based epithelial adhesion and cell matching during Drosophila dorsal closure. Current Biology 10, 11420-1426.
Jacinto, A., Martinez Arias, A. and Martin, P. (2001)
Mechanisms of epithelial sealing and repair.. Nature Cell Biol. 3, E117-E123.
Jacinto, A., Wood, W., Woolner, S., Hiley, C., Turner, L., Wilson, C., Martinez Arias, A. and Martin, P. (2002)
Dynamic analysis of actin cable function during Drosophila dorsal closure. Curr. Biol.12, 1-20.
Kaltschmidt, J. and Martinez Arias, A. (2002)
A new dawn for an old connection: development meets the cell. Trends in Cell Biol. 12, 316-320.
Kaltschmidt, J., Lawrence, N., Morel, V., Balayo, T., Garcia Fernandez, B., Pelissier, A. Jacinto, A., and Martinez Arias, A. (2002)
Planar polarity and actin dynamics in the epidermis of Drosophila. Nature Cell Biology 4, 937-944.
Morel, V. and Martinez Arias, A. (2004)
Armadillo-catenin dependent Wnt signalling is required for the polarisation of epidermal cells during dorsal closure in Drosophila. Development 131, 3273-3283.
Garcia Fernandez, B., Martinez Arias, A. and Jacinto, A. (2007)
Dpp signalling orchestrates dorsal closure by regulating cell shape changes both in the amnioserosa and in the epidermis. Mech. Dev. 124, 884-897.
Gorfinkiel, N. and Martinez Arias, A. (2007)
Requirements for adherens junction components in the interaction between epithelial tissues during dorsal closure in Drosophila. J Cell Sci 120, 3289-3298.
Gorfinkiel, N., Blanchard, G., Adams, R. and Martinez Arias, A (2008)
Mechanical constraints pattern cellular behaviour during Dorsal Closure in Drosophila. Submitted.