Connexin 43 Is Necessary for Salivary Gland Branching Morphogenesis and FGF10-induced ERK1/2 Phosphorylation.

Cell-cell interaction via the gap junction regulates cell growth and differentiation, leading to formation of organs of appropriate size and quality. To determine the role of connexin43 in salivary gland development, we analyzed its expression in developing submandibular glands (SMGs). Connexin43 (Cx43) was found to be expressed in salivary gland epithelium. In ex vivo organ cultures of SMGs, addition of the gap junctional inhibitors 18α-glycyrrhetinic acid (18α-GA) and oleamide inhibited SMG branching morphogenesis, suggesting that gap junctional communication contributes to salivary gland development. In Cx43(-/-) salivary glands, submandibular and sublingual gland size was reduced as compared with those from heterozygotes. The expression of Pdgfa, Pdgfb, Fgf7, and Fgf10, which induced branching of SMGs in Cx43(-/-) samples, were not changed as compared with those from heterozygotes. Furthermore, the blocking peptide for the hemichannel and gap junction channel showed inhibition of terminal bud branching. FGF10 induced branching morphogenesis, while it did not rescue the Cx43(-/-) phenotype, thus Cx43 may regulate FGF10 signaling during salivary gland development. FGF10 is expressed in salivary gland mesenchyme and regulates epithelial proliferation, and was shown to induce ERK1/2 phosphorylation in salivary epithelial cells, while ERK1/2 phosphorylation in HSY cells was dramatically inhibited by 18α-GA, a Cx43 peptide or siRNA. On the other hand, PDGF-AA and PDGF-BB separately induced ERK1/2 phosphorylation in primary cultured salivary mesenchymal cells regardless of the presence of 18α-GA. Together, our results suggest that Cx43 regulates FGF10-induced ERK1/2 phosphorylation in salivary epithelium but not in mesenchyme during the process of SMG branching morphogenesis.

Eye-Mouth Associated Movement in the Human Newborn and Very Young Infant.

BACKGROUND: The aim of this study is to demonstrate that goal-directed eye-mouth associated movement exists in the newborn and very young infant. METHODS: The participants were 17 healthy term newborns or very young infants whose ages at the time of the first examination ranged from 1 to 24 days. The examiner held the tip of an index finger 20 to 30 cm in front of a participant's mouth, then suddenly moved it directly toward the mouth. Thirteen of the participants were also examined with the examiner's palm as the visual stimulus. The response was judged to be positive if clear mouth opening was elicited as the fingertip or palm was approaching the mouth. RESULTS: In the examinations using a fingertip, the frequency of a positive response as to the total number of examinations in the different age groups within the first two months of life ranged between 43.9% and 48.8%, and precipitously decreased to 6.3% at two months of age. A positive response was not elicited from age three months. On the other hand, in the examinations using a palm, the frequency of a positive response was 5.0% in the newborns, and 6.7% in the infants aged between seven days and one month. A positive response was never obtained from two months of age. CONCLUSION: This study demonstrated that visually guided mouth opening toward an approaching target exists in the human newborn. The eye-mouth associated movement may be controlled through rudimentary but functional visuomotor circuits in the brain interconnecting different cortices.