GLI, A ZINC-FINGER TRANSCRIPTION FACTOR AND ONCOGENE, IS EXPRESSED DURING NORMAL MOUSE DEVELOPMENT

The oncogene GLI is amplified and expressed in some cases of human mal ignant glioma and undifferentiated childhood sarcoma and is the protot ype for a gene family characterized by a highly conserved set of five tandem zinc fingers and a consensus cysteine-histidine link. This zinc finger motif has been shown to bind DNA with sequence specificity and may mediate transcriptional regulation. Since GLI is expressed in emb ryonal carcinoma cell lines but not in most normal adult tissues and s hows significant sequence similarity within its zinc finger domain to cubitus interruptus dominant (ci(D)), a Drosophila segmentation gene k nown to be important in the morphogenesis of the posterior portion of each larval segment, we established the temporal and tissue expression patterns of the mouse homologue of human GLI in day 10 through 18 mou se embryos with Northern blotting, reverse transcriptase coupled PCR, and in situ hybridization. gli transcripts were demonstrated on days 1 0 through 18 of mouse embryonic development as well as in normal adult uterus, brain, testis, and limb. Tissue expression of gli during gest ation was demonstrated in Meckel's precartilage mesenchyme, the basis occipitus, rib mesenchymal condensations, primordial vertebral bodies, digital mesenchymal condensations in forefoot and hindfoot plates, th e ependymal layer of the spinal cord, and the mesoderm of the gastroin testinal tract. Expression persisted throughout gestation in developin g bone and cartilage of the extremities, the ribs, and the vertebral b odies, as well as the gastrointestinal tract mesoderm. These findings support a role for gli family genes in normal craniofacial and digital development in mammals first suggested by the demonstration of transl ocation breakpoints within the GLI3 gene in families with the Greig ce phalopolysyndactyly syndrome and subsequently by reduced gli3 expressi on in the mouse mutant extra toes. It is surprising that a single gene would be expressed in such a wide range of mesenchymal structures. (C ) 1993 Wiley-Liss, Inc.