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Hox genes and the molecular basis of vertebrate development

English title Hox genes and the molecular basis of vertebrate development
Applicant Duboule Denis
Number 102277
Funding scheme Project funding (Div. I-III)
Research institution Département de Génétique et Evolution Faculté des Sciences Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Embryology, Developmental Biology
Start/End 01.10.2003 - 30.09.2008
Approved amount 1'301'596.00
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Keywords (4)

hox; genes; molecular basis; vertebrate development

Lay Summary (English)

Lead
Lay summary
Hox genes and vertebrate morphogenesisWe are interested in the regulatory mechanisms underlying vertebrate pattern formation, in both developmental and evolutionary contexts. For the past years, we have focused on Hox genes, a family of transcription factors that display special paradigmatic values, regarding their regulatory strategies, their functional organization and their key roles in morphological evolution. In the course of our last FNRS granting period, we initiated an ambitious program aimed at genetically dissecting these various aspects of Hox gene biology, either using the potential of established mouse genetic manipulations, or by designing and implementing a powerful strategy relying upon inter chromosomal meiotic recombination (TAMERE). This grant proposal is concerned with both the continuation of successful lines of research, and the start of novel projects, mostly concerned with high throughput technologies applied to mouse genetics. These research projects are all devoted to three major aspects of Hox genes biology, i.e. their regulation, their functions and their evolutionary relevance.A) Regulation 1We would like to understand the mechanistic basis of colinearity, i.e. the mechanism by which neighboring genes are activated one after the other in overlapping anterior to posterior domains in the trunk. This correspondence between the linearity of chromosomes and our body architecture is still an enigma and we believe our strains of mice as well as our novel approaches to engineer chromosomes can help revolving it.B) FunctionWe shall continue our attempts to unravel the functions of Hox genes by using a series of tools we have constructed over the past four years. Because of both the large redundancy observed in this gene family, and compensatory mechanisms, multiple gene knock-out will be necessary to precisely evaluate the function of these genes. This can only be done using conditional systems. These genes have crucial functions, not only during development, but also in the physiology of the animal and many human disorders have been attributed to mis-functions of Hox genes.C) EvolutionWe will also continue to explore the involvement of Hox genes in morphological evolution, at the levels of both the modification of regulatory controls, and the resulting variations in the functional deployment of HOX proteins and their impacts upon the emergence of novel structures in the course of vertebrate phylogeny. We would like to propose explanations regarding the mechanisms underlying major evolutionary novelties, in particular with respect to the emergence of tetrapod appendages.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
122008 Hox genes and the molecular bases of vertebrate development 01.10.2008 Project funding (Div. I-III)
53527 Hox genes and the molecular basis of vertebrate development 01.10.1998 Project funding (Div. I-III)

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