Promoter region of the human GLI gene functions in mouse embryos

GLI is the prototype for the Gli-Knippel gene family characterized by a consensus C2-H2 zinc finger domain. The family includes the developmental regulatory genes Drosophila ci, C. elegans tra-1 and human and mouse GLI3. GLI is believed to function as a developmental regulatory gene based on its highly conserved zinc finger domain and the restricted pattern of expression of mouse gli within primitive mesenchyme and the developing central nervous system during mouse embryonic development. In this work, the ability of potential transcriptional regulatory elements in the human GLI promoter region to drive reporter gene expression in vitro and in vivo was tested by transfection analysis of Tera-1 cells and by microinjection to produce transgenic mice. A 450 bp segment drove expression of a luciferase reporter gene maximally in Tera-1 cells defining a human GLI core promoter region. In vivo analysis showed that a 1.45 kb upstream segment of human GLI, including the core promoter region, directed ß-gal expression to the central nervous system at E11.5, and to most sites of endochondral ossification at E12.5. This pattern driven by the human GLI promoter in the mouse embryo is comparable to the expression pattern of mouse gli during mouse embryonic development. The full length cDNA sequence of mouse gli was identified and it demonstrates 85% homology with the full length human GLI transcript at the amino acid level. The highly homologous sequence of the human and mouse GLI transcripts and the ability of the human GLI promoter to drive reporter gene expression in the mouse embryo in a comparable pattern to mouse gli expression pattern during development, show that the gene transcripts as well as their control elements are highly conserved between the human and the mouse.