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.
Kim
Jae-Young
JY
Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, College of Dentistry, Brain Korea 21 Project for Medical Science, Yonsei Center of Biotechnology, Yonsei University, Seoul, South Korea. hsjung@yumc.yonsei.ac.kr
Cho
Sung-Won
SW
Lee
Min-Jung
MJ
Hwang
Heui-Jung
HJ
Lee
Jong-Min
JM
Lee
Syng-Ill
SI
Muramatsu
Takashi
T
Shimono
Masaki
M
Jung
Han-Sung
HS
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002352:Carrier Proteins / Q000096:biosynthesis; D018031:Connexin 43 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D051379:Mice; D008813:Mice, Inbred ICR; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009924:Organ Culture Techniques; D014059:Tongue / Q000196:embryology / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D018031:Connexin 43; D053823:Hedgehog Proteins; D016376:Oligonucleotides, Antisense; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C465570:Shh protein, mouse