EXPRESSION OF HOMEO-BOX CONTAINING GENES DURING EARLY XENOPUS DEVELOPMENT

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Homeobox containing genes are a family of genes which have been shown in Drosophila to control pattern formation during development. These genes encode proteins which bind to DNA in a sequence specific manner. They contain a 180 bp conserved DNA domain called a homebox. Mutations in some of these genes cause "homeotic" transformation, in which one part of the body develops in the likeness of another. Homeobox genes although best studies in Drosophila, have been identified in a variety of species including frogs, mice, and man. We have isolated several homeobox containing genes which are activated during early Xenopus development. We have determined their temporal and spatial expression pattern using Northern blot analysis and in situ hybridization. At least some of these genes are expressed during gastrulation, a critical time period of development at which mesodermal and neural induction takes place. Sequence analysis of these genes revealed that some of them are homologous to previously described genes in other species such as mouse and Drosophila, others have not yet been described. One of the genes which is homologous to the Drosophila Distal-less gene is likely to be involved in limb formation and regeneration. Another gene, which shows a highest homology to the murine Oct-3 gene is a good candidate to be a general transcriptional activator during early frog development. This gene is expressed in the ovary, and its RNA is localized preferentially in the animal half of the embryo. This gene might be involved in establishment of ectoderm specific gene transcription. The ultimate goal of the project is to understand how the normal developmental pattern is established and which of the genes play a critical role in this process. Understanding of these processes in frog will give us a better understanding of developmental malformations in humans.