Meeting Abstract
P1.122 Thursday, Jan. 3 Functional sequence divergence between coparalogous fugu Hoxa2 enhancers ALEXANDER, T.B.*; TUMPEL, S.; WEIDEMANN, L.M.; KRUMLAUF, R.; Stowers Institute for Medical Research, Kansas City, MO tba@stowers-institute.org
In higher vertebrates, Hoxa2 functions to impart anteroposterior positional identity and patterning information to specific cranial segments during development. In contrast to the highly conserved expression pattern of Hoxa2 in tetrapods, spatiotemporal expression pattern variations have been reported in numerous teleost species. An additional round of Hox cluster duplication in teleosts has likely contributed to the continued evolution of Hox genes in these species. To better understand the evolutionary processes generating expression pattern divergence, we are investigating the cis-regulatory basis for the differential expression of the two fugu (Takifugu rubripes) coparalogous Hoxa2 genes, Hoxa2a and Hoxa2b. Fugu cis-regulatory elements were identified based on sequence conservation to known mouse enhancers and functional testing using transgenic mouse reporter assays. Interestingly, the two fugu Hoxa2 enhancers tested contained converse regulatory potential in the hindbrain and neural crest: the Hoxa2a enhancer directed neural crest, but not hindbrain, expression, while the Hoxa2b enhancer regulated only hindbrain expression. In this study, we investigate the sequence changes responsible for the differential neural crest activity of these enhancers. We have identified a critical region within the Hoxa2a enhancer required for cranial neural crest expression. We show that switching this module into the context of the Hoxa2b enhancer is sufficient to provide it with some neural crest activity. Surprisingly, the functionally critical region defined by our studies does not correspond to any of the known mouse neural crest regulatory modules. Continued investigation into the sequence changes responsible for the differential regulatory potential of these two enhancers will likely provide insight into the mechanisms involved in cis-regulatory evolution.
