Evolution, Function and Regulation of Teleost Hox Genes

University Of Chicago, Chicago IL

Investigators

Abstract

0091101 Prince The Hox genes set up pattern along the anteroposterior axis of developing metazoan embryos. Hox cluster duplication events accompanied vertebrate origins and provided additional patterning information, likely allowing for more complex body plans to arise. Recent work from the P.I. and others has established that in the teleost lineage an additional genome duplication event has led to significant differences between the Hox organization and complement of tetrapods and teleosts. This study will focus on zebrafish hox genes in the anteriorly expressed paralogue group (PG) 1 as a paradigm to compare and contrast gene function and regulation in different vertebrate groups and hence to investigate Hox gene modification during evolution. Preliminary studies have shown that the zebrafish PG1 hox genes are significantly different in terms of organization, expression, and potential function, from those of the tetrapod vertebrates such as mouse. Thus, zebrafish hoxa1a is expressed in a completely different manner to the orthologous mouse Hoxa-1 gene, having a novel anterior expression domain in the ventral midbrain. Furthermore, midbrain expression is shared by medaka, a distantly related teleost species. This study will take a broader comparative approach to determine when in vertebrate evolution this anterior expression arose. Conversely, the zebrafish hoxb1b gene has an expression pattern remarkably similar to that of the non-orthologous mouse Hoxa-1 gene. Preliminary experiments have established that mis-expression of PG1 genes causes a classic posteriorizing homeotic transformation of the hindbrain. Together these data suggest the hypothesis that zebrafish hoxb1b is functionally equivalent to mouse Hoxa-1; this hypothesis will be tested directly using a novel loss-of-function approach based on antisense morpholino RNAs. A similar approach will be used to test redundancy or synergy of function with the duplicate gene hoxb1a.