Cooperative Group in Organogenesis, Growth and Regeneration

Lead Research Organisation: University of Bath
Department Name: Biology and Biochemistry

Abstract

The title of the Coop indicates a focus on organogenesis, growth and regeneration . Organogenesis means the later stages of embryonic development during which individual organs are formed and develop to the stage at which they can perform their specific function. Growth means increase in size, either of the whole body or of a part relative to the rest. Regeneration means the ability to regrow a body part that has been removed or damaged.
We are interested in various aspects of these processes. Firstly, what distinguishes the different tissue types of, for example, the gut ? We have found that certain master genes can convert pancreas to liver and liver to pancreas and we intend to find new ways of interconverting tissues, based on our knowledge of normal development. Secondly, how is the structure of a tissue related to growth ? Tissues are organised into structural-proliferative units such as the crypts of the intestine. We are interested in the genes that govern the formation and behaviour of these units. Thirdly, we are interested in what makes one sort of cell different from another. Organs usually contain several cell types, arising from a single type of stem cell, and we wish to find what governs the proportions of different types that are formed and the spatial pattern they assume. Fourthly, the genes that control growth are often only active if they have been inherited from one particular parent. We are interested in what causes this restriction and how various diseases arise when the control breaks down. Fifthly, we know that the genetic material is organised in a particular way because of its evolutionary history. We hope to be able to predict the degree of genetic damage from knowing in which tissues genes are normally active. Lastly, we are trying to understand the mechanisms behind the ability of lower animals to regenerate missing structures. We have devised new methods for modifying the activity of specific genes, and visualising specific cell populations during tail regeneration. Using the tadpole tail as a model, we are beginning to be able to inhibit regeneration where it occurs and to activate it where it does not normally occur.
Understanding how the body normally carries out these processes should enable us to modify them and in particular to seek new treatments for conditions in which organs or tissues are damaged by injury or disease.

Technical Summary

1. Investigation of gut development using microsurgical and genetic methods. Regional specification in endoderm, origin of crypt organisation (Slack, Hassan).
2. Cell differentiation and transdifferentiation: investigating the molecular basis of experimental and pathological transdifferentiation, particularly interconversions between endoderm-derived epithelial tissues such as thyroid, lung, liver, pancreas, and intestine, and between neural crest derivitives (Tosh, Slack, Kelsh).
3. Development and pathology of the liver (Tosh)
4. Regeneration of limbs and tails in Xenopus tadpoles. The use of transgenic methods to reprogramme organisms to enhance or reduce regenerative ability (Slack).
5. Tracing cell lineage in appendage regeneration and in neural crest development (Slack, Kelsh).
6. Neural crest pattern formation. Pigment pattern and ganglial development (Kelsh).
7. Sox10, otic development and deafness in Waardenburg-Shah syndrome (Kelsh, Ward).
8. Biochemistry and cell biology of IGF2 and insulin signalling (Holman)
9. Relationship of imprinting to normal growth control. Especially in relation to role of IGF2 and Grb10 systems (Ward, Hurst, Hassan, Holman).
10. Relationship of IGF2 system to genetic and acquired pathologies of growth: dysplasia, hyperplasia and neoplasia; tumour progression (Hassan, Ward).
11. Relationship between genome organisation, tissue specific gene activity, and frequency of mutation (Hurst).

Publications

10 25 50
 
Description Daly group 
Organisation The Garvan Institute for Medical Research
Country Australia 
Sector Hospitals 
PI Contribution Sharing of mouse genetic resources and data generated from the analysis of these resources
Collaborator Contribution Sharing of mouse genetic resources and expertise in their analysis
Impact Publications: PMID: 17562854 PMID: 19541746
 
Description Malik group 
Organisation University of Bristol
Department School of Social and Community Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Sharing of mouse genetic resources and data from the analysis of these resources
Collaborator Contribution Sharing of data and resources
Impact Publications: PMID: 17940140 PMID: 19956686
 
Description Pavan Group 
Organisation George Washington University
Country United States 
Sector Academic/University 
PI Contribution Sharing of mouse genetic resources and data from the analysis of these resources
Collaborator Contribution Access to novel bioinformatic tools; analysis of our mouse genetic resources
Impact Publications: PMID: 16330480 PMID: 18950534