Morphogenesis

Research Interests

Cell and Developmental Biology, Morphogenesis, Cell Adhesion, Wound Healing, Dorsal Closure, Drosophila Genetics.

Group Members

Research Project

Epithelial dynamics and adhesion during Drosophila dorsal closure

The movement and adhesion of epithelial sheets are fundamental morphogenetic processes that occur throughout embryogenesis and whenever a tissue is wounded in the adult organism. In humans, defects in epithelial movement and adhesion can be the cause for clinical conditions such as spina bifida and palate clefts in newborns. Dorsal closure is a morphogenetic movement during Drosophila development that provides a genetically tractable model of cell spreading, cell-cell recognition and adhesion. During this process two opposing epithelial fronts move dorsally to form a neat seam closing over the dorsal surface of the embryo REF. We are combining Drosophila genetics and advanced imaging techniques to investigate dorsal closure: (1) to analyse mutant phenotypes at the cellular level to further elucidate the function of Drosophila genes already known to be involved in this process; (2) to test the function of adhesion/recognition related candidate genes, such as members of the cadherin gene family; (3) to develop genetic screens to identify new genes involved in cell-cell recognition and adhesion during (4) to identify novel components of the cell-cell recognition and adhesion system during dorsal closure using proteomics and genomics.

Funding

POCTI/BCI/41909/2001
Epithelial dynamics and adhesion during Drosophila dorsal closure

Collaborators

Department of Genetics, University of Cambridge, UK
Alfonso Martinez Arias

Research Project

Wound repair using Drosophila as a model system

The capacity to repair an epithelial wound is a fundamental survival mechanism that can be activated at any site of damage throughout embryonic and adult life. During embryogenesis, several morphogenetic movements, such as dorsal closure, closely resemble the artificially activated tissue movements of wound healing. Understanding how epithelia move and fuse together in these embryonic situations may reveal clues as to how these same processes are accomplished during tissue repair and provide a way in which we might modulate wound healing. We are investigating how far the similarities between dorsal closure and wound healing extend by using what we know about gene cascades regulating morphogenetic movements in Drosophila, to dissect out which genes may also be necessary for the cell and tissue movements that occur in wound repair. We have established an embryonic wounding assay using a laser ablation system that has allowed the initial characterisation of epithelial wound healing in wild-type Drosophila embryos using confocal microscopy. It is now possible to test which of the factors that are involved in dorsal closure are also functionally required to initiate or drive the wound closure. We are using our wounding system to test mutants defective for morphogenetic genes that may be required during wound healing.

Collaborators

University College London, UK
Paul Martin

Research Project

Drosophila hemocyte recruitment to wound sites

During wound healing in vertebrates the inflammatory leukocytes, such as neutrophils and macrophages, act to clear contaminating microrganisms and debris, and to amplify the earlier wound signals by the release of further pro-inflammatory factors, which instruct neighbouring cells, mainly fibroblasts and keratinocytes, to contribute to the repair process. Several of the chemoattractants that can recruit blood cells to the wound site have been identified. However, the exact regulation of this process is not understood and the mechanisms that act in vivo are difficult to unravel due to the number of factors involved and complexity of interactions between the different cell types. Studies in simpler models like Drosophila are expected to reveal some of the fundamental mechanisms of cell recruitment to wounds. Our laser ablation wounding system is used to test the function of factors potentially involved in hemocyte chemoattraction, that have homologues in flies.

Collaborators

University College London, UK
Paul Martin

Research Project

A gain of function screen to identify the molecular basis of epithelial adhesion, contact inhibition and cell:cell matching during Drosophila dorsal c

Funding

Travel-Collaborative grant 069880
A gain of function screen to identify the molecular basis of epithelial adhesion, contact inhibition and cell:cell matching during Drosophila dorsal closure and wound repair

Publications

Jacinto, A. and Baum, B. (2003). Actin in Development. Mech Dev 120 :1337-1349

Wood, W. and Jacinto, A. (2003). Imaging cell movement during dorsal closure in Drosophila embryos, in Cell Migration in Development - Methods in Molecular Biology (Guan, J.L., ed.), Humana press, in press.

Jacinto, A., Woolner, S. and Martin P. (2002). Dynamic analysis of dorsal closure in Drosophila – from genetics to cell biology. Dev Cell 3 :9-19

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 :1245-1250

Wood, W., Jacinto, A., Grose, R., Gale, J., Wilson, C. and Martin, P. (2002). Wound healing recapitulates morphogenesis , co-ordinated regulation of actin cytoskeletal elements by small GTPases during repair of epithelial wounds in Drosophila embryos. Nat Cell Biol 4 :907-912

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. Nat Cell Biol 4 :937-944

Jacinto A., Martinez-Arias A., Martin P. (2001). Mechanisms of epithelial fusion and repair. Nat Cell Biol 3 :E117-23

Jacinto, A., Wood, W., Balayo, T., Turmaine, M., Martinez-Arias, A., Martin, P. (2000). Dynamic actin-based epithelial adhesion and cell matching during Drosophila dorsal closure. Curr Biol 10 :1420-1426

Alexandre, C., Jacinto, A. and Ingham, P.W. (1996). Transcriptional activation of hedgehog target genes in Drosophila is mediated by the Cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins. Genes & Dev. 10 :2003-2013

Fietz, M.I., Jacinto, A., Taylor, A.M., Alexandre, C. and Ingham, P.W. (1995). Secretion of the amino-terminal fragment of the Hedgehog protein is necessary and sufficient for hedgehog signaling in Drosophila. Curr. Biol. 5 :643-650