CONTROL OF COLINEARITY IN ABDB GENES OF THE MOUSE HOXD COMPLEX

During development, vertebrate Hox genes are activated in a temporal a nd spatial sequence colinear with the position of the genes within the ir clusters. To investigate the mechanistic basis of this phenomenon, we used the ES cell technology and the loxP/Cre system to engineer a c onditional fusion of the 5' exon of Hoxd-13 with the 3' exon of Hoxd-1 2. This hybrid transcription unit was regulated like Hoxd-11, with exp ression limits in the trunk, limbs, intestinal, and urogenital systems more anterior than those expected for either Hoxd-13 or Hoxd-12. An i n vivo interspecies replacement by the fish homologous DNA fragment sh owed that anteriorization was not due to a distance effect, thus sugge sting the presence of a regulatory element between Hoxd-13 and Hoxd-12 that may contribute to the establishment, early on, of a repressive s tate over these two genes.