HOXB-13 - A NEW HOX GENE IN A DISTANT REGION OF THE HOXB CLUSTER MAINTAINS COLINEARITY

The Hox genes are involved in patterning along the A/P axes of animals , The clustered organization of Hox genes is conserved from nematodes to vertebrates, During evolution, the number of Hox genes within the a ncestral complex increased, exemplified by the five-fold amplification of the AbdB-related genes, leading to a total number of thirteen para logs, This was followed by successive duplications of the cluster to g ive rise to the four vertebrate HOX clusters, A specific subset of par alogs was subsequently lost from each cluster, yet the composition of each cluster was likely conserved during tetrapod evolution, While the HOXA, HOXC and HOXD clusters contain four to five AbdB-related genes, only one gene (Hoxb-9) is found in the HOXB complex, We have identifi ed a new member of paralog group 13 in human and mouse, and shown that it is in fact Hoxb-13. A combination of genetic and physical mapping demonstrates that the new gene is found approx, 70 kb upstream of Hoxb -9 in the same transcriptional orientation as the rest of the duster, Despite its relatively large distance from the HOX complex, Hoxb-13 ex hibits temporal and spatial colinearity in the main body axis of the m ouse embryo, The onset of transcription occurs at E9.0 in the tailbud region. At later stages of development, Herb-13 is expressed in the ta ilbud and posterior domains in the spinal cord, digestive tract and ur ogenital system, However, it is not expressed in the secondary axes su ch as the limbs and genital tubercle. These results indicate that the 5' end of the HOXB cluster has not been lost and that at least one mem ber exists and is highly conserved among different vertebrate species, Because of its separation from the complex, Hoxb-13 may provide an im portant system to dissect the mechanism(s) responsible for the mainten ance of colinearity.