Inhibition of connexin 43 alters Shh and Bmp-2 expression patterns in embryonic mouse tongue.

The morphogenesis of fungiform papillae occurs in a stereotyped pattern on the dorsal surface of the mammalian tongue via epithelial-mesenchymal interactions. These interactions are thought to be achieved via intercellular communication. Gap junctions can be observed in many developing tissues and have been suggested to participate in a variety of functions, including the regulation of cell proliferation, differentiation, and apoptosis. Here, we demonstrate that the expression of Connexin 43 (Cx43), a gap junction protein, is correlated significantly with the development of fungiform papillae, which exhibit a pattern formation and morphogenesis similar to the development of other epithelial appendages. Antisense-oligodeoxynucleotide (AS-ODN) against Cx43 was used to assess the developmental functions of Cx43. The expression patterns of the signaling molecules were disrupted by Cx43 inhibition. Interestingly, the expression patterns of Shh, a key molecule in the determination of the spacing patterns of fungiform papillae, were disturbed after treatment with Cx43 AS-ODN. We have also attempted to determine the functions of Bmp-2 by applying NOGGIN protein to tongue cultures. Our results indicate that upstream regulation via Cx43 controls the Shh and Bmp-2 pathways for the morphogenesis and pattern formation of fungiform papillae.