Interspecies exchange of a Hoxd enhancer in vivo induces premature transcription and anterior shift of the sacrum.
The precise activation, in space and time, of vertebrate Hox genes is an essential requirement for normal morphogenesis. In order to assess for the functional potential of evolutionary conserved Hox regulatory sequences, a phylogenetically conserved bipartite regulatory element necessary for proper spatial and temporal activation of the Hoxd-11 gene was replaced by its fish counterpart in the HoxD complex of mice, using an ES cell-based targeted exchange. Fetuses carrying this replacement activated Hoxd-11 transcription prematurely, which led to a rostral shift of its expression boundary and a consequent anterior transposition of the sacrum. These results demonstrate the high phylogenetic conservation of regulatory mechanisms acting over vertebrate Hox complexes and suggest that minor time difference (heterochronies) in Hox gene activation may have contributed to important morphological variations in the course of evolution.
Gérard
M
M
Department of Zoology and Animal Biology, University of Geneva, Sciences III, Switzerland.
Zákány
J
J
Duboule
D
D
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004274:DNA, Recombinant; D005314:Embryonic and Fetal Development; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D005801:Genes, Homeobox / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D012447:Sacrum / Q000196:embryology*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins
D004274:DNA, Recombinant; D018398:Homeodomain Proteins; C490939:Hoxd11 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D029961:Zebrafish Proteins; C099221:hoxd11a protein, zebrafish