3016 The Role of E-cadherin in Submandibular Gland Development
S. KHALIL1, M. KUKURUZINSKA1, M. HOFFMAN2, J. WALKER3, A.S. MENKO4, and I. REBUSTINI2, 1Boston University, MA, USA, 2NIDCR, Bethesda, MD, USA, 3Thomas Jefferson University, Philadelphia, PA, USA, 4Thomas Jefferson University, Philadelphia, USA

Objectives: The submandibular gland (SMG) develops through branching morphogenesis from an epithelial bud into an array of ducts terminating in the secretory acini. Here, we demonstrate essential roles for E-cadherin in the formation of acinar and ductal structures.

Methods: Mouse submandibular glands were isolated and cultured.

Results: Immunofluorescence staining of F-actin, Ki67 and a neonatal acinar marker B1 revealed three cell populations in the developing buds: 1) the outer layer with proliferative polarized acinar progenitors, 2) the adjacent proliferative unpolarized cells, and 3) the nonproliferative differentiating duct cells. E-cadherin was essential for new bud formation because function blocking antibodies against E-cadherin ectodomains (ECs), EC1, EC2 and EC5 suppressed budding. E-cadherin was required for the expansion of acinar progenitors and the adjacent cells since antibodies to EC5 inhibited proliferation. E-cadherin was also critical for the survival of differentiating duct cells, since antibodies to EC2 and EC5 abolished duct development and induced apoptosis.

Conclusion: These data provide insights into E-cadherin functions during SMG development and suggest that different ectodomains mediate distinct cellular responses.

Grant sponsor: NIH; Grant number: DE014437, DE010183

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