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Hox gene regulation and function within the neural tube

Reference	BBS/E/B/21001026
Principal Investigator / Supervisor	Dr Stephen Gaunt
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	154,372
Status	Completed
Type	Institute Project
Start date	01/04/1997
End date	31/03/2000
Duration	36 months

Abstract

Hox gene expression domains establish regional differences within the developing embryo. Our recent work indicates (i) that final positions of Hox boundaries arise as a result of local tissue interactions, (ii) that shifts in Hox boundaries play a role in evolutionary changes in body shape (specifically, Hoxc-6 boundary in chicken is shifted posteriorly relative to mouse), (iii) that Hox cluster regions that have lost homeoboxes may still generate some transcripts. We will explore further these findings by (i) testing plasticity of Hox expression in transposed neural tube and mesoderm fragments, (ii) examining Hox boundaries generated by chick Hoxc-6 in transgenic mice (to elucidate mechanisms of evolutionary Hoxc-6 shift), (iii) testing whether transcribed regions from missing Hox genes follow, in neural tube, established rules for Hox expression (colinearity in order of genes and their transcripts). The project is relevant to the H&LS Foresight in that it will contribute to an understanding of (i) Neurosciences (molecular and cellular neurobiology), (ii) Genetics in Risk Evaluation and Management (role of Hox genes in developmental programming ), (iii) Diagnostic Applications of Molecular Biology (role of Hox genes in congenital abnormalities with opportunities for diagnostic markers) and (iv) Integrative Biology (since Hox genes, being master control genes, may also directly or indirectly impinge upon many other aspects of biology, in health and disease)and this . This is a multidisciplinary project combining gene (DNA) analysis with tissue transplantation studies (in chick embryo) and transgenic studies (in mice). The questions it poses span the fields of both developmental and evolutionary biology. The likely benefit of the research is enhanced understanding at the molecular and cellular levels of mechanisms for the establishment of Hox gene expression patterns within both neural tube and mesoderm- derived tissues of the developing embryo. The work should elucidate evolutionary mechanisms which have resulted in Hox boundaries becoming shifted (enabling development of new body designs) and Hox genes becoming selectively lost. The potential exploitability of the work lies in producing a background of information likely to be essential in further studies on analysis of birth defects and congenital abnormalities.

Summary

unavailable

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

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