title: E-cadherin can replace N-cadherin during secretory-stage enamel development.
abstract: BACKGROUND
  N-cadherin is a cell-cell adhesion molecule and deletion of N-cadherin in mice is embryonic lethal. During the secretory stage of enamel development, E-cadherin is down-regulated and N-cadherin is specifically up-regulated in ameloblasts when groups of ameloblasts slide by one another to form the rodent decussating enamel rod pattern. Since N-cadherin promotes cell migration, we asked if N-cadherin is essential for ameloblast cell movement during enamel development.
  
  
  RESULTS
  The enamel organ, including its ameloblasts, is an epithelial tissue and for this study a mouse strain with N-cadherin ablated from epithelium was generated. Enamel from wild-type (WT) and N-cadherin conditional knockout (cKO) mice was analyzed. μCT and scanning electron microscopy showed that thickness, surface structure, and prism pattern of the cKO enamel looked identical to WT. No significant difference in hardness was observed between WT and cKO enamel. Interestingly, immunohistochemistry revealed the WT and N-cadherin cKO secretory stage ameloblasts expressed approximately equal amounts of total cadherins. Strikingly, E-cadherin was not normally down-regulated during the secretory stage in the cKO mice suggesting that E-cadherin can compensate for the loss of N-cadherin. Previously it was demonstrated that bone morphogenetic protein-2 (BMP2) induces E- and N-cadherin expression in human calvaria osteoblasts and we show that the N-cadherin cKO enamel organ expressed significantly more BMP2 and significantly less of the BMP antagonist Noggin than did WT enamel organ.
  
  
  CONCLUSIONS
  The E- to N-cadherin switch at the secretory stage is not essential for enamel development or for forming the decussating enamel rod pattern. E-cadherin can substitute for N-cadherin during these developmental processes. Bmp2 expression may compensate for the loss of N-cadherin by inducing or maintaining E-cadherin expression when E-cadherin is normally down-regulated. Notably, this is the first demonstration of a natural endogenous increase in E-cadherin expression due to N-cadherin ablation in a healthy developing tissue.
authors.affiliation: Department of Mineralized Tissue Biology and Harvard School of Dental Medicine, The Forsyth Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Xiaomu
authors.initials: X
authors.lastname: Guan
authors.affiliation: Department of Mineralized Tissue Biology and Harvard School of Dental Medicine, The Forsyth Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Felicitas B
authors.initials: FB
authors.lastname: Bidlack
authors.affiliation: Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, New York, United States of America.
authors.forename: Nicole
authors.initials: N
authors.lastname: Stokes
authors.affiliation: Department of Mineralized Tissue Biology and Harvard School of Dental Medicine, The Forsyth Institute, Cambridge, Massachusetts, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Bartlett
mesh_terms: D000565:Ameloblasts / Q000166:cytology / Q000378:metabolism*; D000566:Amelogenesis / Q000235:genetics*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D003743:Dental Enamel / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D004658:Enamel Organ / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006244:Hardness; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D061251:Primary Cell Culture; D015398:Signal Transduction; D013499:Surface Properties; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D015820:Cadherins; D002352:Carrier Proteins; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C489083:Cdh2 protein, mouse