The morphological and possible functional interactions between the connective tissue and epithelial elements of enamel organ were examined during the maturation phase, using immunohistochemical techniques. Decalcified mandibular sections (10µm) including incisors from Wistar rats ages 10–12 weeks were used. Sections were incubated with one or two primary antibodies targeting cell cytoskeleton (vimentin, α-actin, α-tubulin), dendritic marker (OX6), gap junctions (cx-43), enzymes (nitric-oxide

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... thase (nos1) and cyclooxygenase (cox1)), and ion transporters (Na+/H+ exchanger (NHE1) and Na+/Ca2+ exchanger (NCX)) for 24h, before incubation with the appropriate conjugated fluorescent secondary antibodies. Sections were then examined by fluorescence microscopy. Haematoxylin-eosin slides were also employed. Cellular heterogeneity and morphological modulations were identified within the epithelial and connective tissue elements of the enamel organ suggesting complex cellular interactions and indicating the use of enamel organ term to represent all these regions. Also, some ion transportation activity, and nos1 and cox1 signalling pathways have been identified, indicating intercellular communication between these regions. A hypothesis was suggested, to explain the morphological modulation of ameloblasts and papillary cells during enamel maturation aimed to increase the transporting membrane surface area to accomplish faster and bulker ion transportation to achieve controlled pH and to direct Ca2+ towards enamel. Connective tissue covering epithelial cells of the enamel organ showed morphological and physiological interaction during enamel maturation, suggesting new functional concepts.