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Functional comparative Genomics and loss of function study of Vertebrate Iroquois A Genes


The Iroquois (Irx) genes participate in numerous events during vertebrate neural development, such as antero-posterior and dorso-ventral subdivision of the developing nervous system. However, most of the information about their function and regulation still remains unknown.

Mammalian Irx genes are arranged in two clusters, IrxA and IrxB, containing three genes each. To understand the role of Irx during development it is imperative to unravel the regulatory networks in which these clustered genes are immerse d. Dr. Gómez-Skarmeta group (CABD, Seville) has taken advantage of the availability of whole genome sequences for a number of vertebrate model systems to identify putative enhancers within the Irx clusters.

By using evolutionary conservation as a guide for important genomic sequences, they have found many conserved non-coding regions located along both Irx clusters (unpublished data). I wish to incorporate to his group and focus in the study of function and regulation of the Iroquois A cluster.

The purpose of this project is:
- To examine whether the conserved regions harbour specific enhancers in vertebrates (mouse, Xenopus, zebrafish) using genomic comparison and generating transgenic animals with these regions;
- To characterize the regulatory and signalling pathways that act on some of these enhancers in different vertebrates by a combination of different biological disciplines and techniques (bioinformatics, animal cap, dominant negative forms);
- To explore the defects associated with loss of function of single, or combinations of, Irx genes using morpholinos in Xenopus tropicalis.

Additionally, in the next future, we will determine whether these elements and the pathways that activate them can be used to differentiate mouse stem cells towards specific neural fates. The study of IrxA function in different vertebrates may help to understand the development of the neural system and of certain human diseases (e.g. cri-du-chat syndrome).

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C/serrano 117

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