Title:
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Comparative and functional analysis of the Msx-1 proximal regulatory region
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Metazoan embryogenesis is characterised by the large scale cellular movements of morphogenesis and the co-ordinated expression of genes specifying pattern in the resultant structures. In Drosophila one family of such genes, the homeobox genes, is involved in some of the key mechanisms effecting these processes. Homeobox genes play a similar role of patterning the body in vertebrate embryos. Msx-1 is one member of a family of three vertebrate homeobox genes homologous to the Drosophila homeobox gene msh. Little is known of the role of the msh gene in Drosophila however detailed analysis of the expression pattern of Msx-1 in the developing mouse has led to the proposal that it is involved, possibly through a role in inductive interactions, in development of the heart, eye, limbs and craniofacial structures. Detection of Msx-1 transcripts by RNA in situ hybridisation demonstrates that precise spatial and temporal regulation of Msx-1 expression is achieved at the transcriptional level. Experiments in the limb show that this regulation responds to positional cues as expected of a gene concerned with patterning the developing body. Knowledge of the mechanisms by which Msx-1 transcription is regulated and identification of the gene products involved is vital to an understanding of the regulatory cascade that patterns the embryo, and to a view of the role of Msx-1 in such a system. To elucidate this problem I have analysed the 5'-flanking region of the gene and attempted to identify cis-acting DNA regulatory elements close to Msx-1. Non-functional parts of the genome are subject to a gradual 'drift' in nucleotide content.
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