N-cadherin is required for cytodifferentiation during zebrafish odontogenesis

N-cadherin is a well-studied classic cadherin involved in multiple developmental processes and is also known to have a signaling function. using the zebrafish (danio rerio) as a model,we tested the hypothesis that tooth morphogenesis is accompanied by dynamic changes in n-cadherin distribution and that absence of n-cadherin disturbs tooth development. n-cadherin,encoded by the gene cdh2,is absent during the initiation and morphogenesis stages of both primary (first-generation) and replacement teeth,as demonstrated by immunohistochemistry. however,n-cadherin is up-regulated at the onset of differentiation of cells of the inner dental epithelium and the dental papilla,i.e.,the ameloblasts and odontoblasts,respectively. in the inner dental epithelium,n-cadherin is co-expressed with e-cadherin,excluding the occurrence of cadherin switching such as observed during human tooth development. while early lethality of n-cadherin knockout mice prevents any functional study of n-cadherin in mouse odontogenesis,zebrafish parachute (pac) mutants,deficient for n-cadherin,survive beyond the age when primary teeth normally start to form. in these mutants,the first tooth forms,but its development stops at the early cytodifferentiation stage. n-cadherin deficiency also completely inhibits the development of the other first-generation teeth,possibly due to the absence of n-cadherin signaling once the first tooth has differentiated. © 2013 international & american associations for dental research.