Transgenic analysis of a potential Hoxd-11 limb regulatory element present in tetrapods and fish

Genes of the HoxD complex related to the Drosophila Abd-B gene are involved in the morphogenesis of vertebrate paired appendages. Hoxd-11, for instance, is necessary in combination with other Hox genes for the proper development of different parts of the tetrapod limbs. Sequence comparisons between the mouse, chicken, and zebrafish Hoxd-11 loci have revealed the conservation of several blocks of DNA sequence which may be of importance for the regulation of Hoxd-11 expression. We have used transgenic mice to show that one of these conserved elements specifically drives expression in a proximal-posterior part of developing forelimbs. Production of mice transgenic for a full fish Hoxd-11 construct as well as for mouse-fish Hoxd-11 chimeric constructs shows that the fish counterpart of this sequence is able to elicit expression in mouse forelimbs as well, though in a slightly different domain. However, this fish element requires the presence of the mouse promoter and does not work in its own context. These results are discussed in light of both the control of Hoxd gene expression during limb development and the use of a comparative interspecies approach to understand the regulation of genes involved in vertebrate development.