The role of [alpha]3[Beta]1 integrin in salivary gland development
Ryan, Tifany T.
MetadataShow full item record
Submandibular gland (SMG) formation is a consequence of reciprocal epithelial-mesenchymal interactions and epithelial differentiation that establish mature duct systems and acini. These processes are governed,in part, by interactions between integrins and their extracellular matrix (ECM) ligands. This thesis studied the role of [alpha]3[Beta]1 integrin in the biogenesis of the SMG. It will be shown that there were severe abnormalities in the SMG from mice with a targeted mutation in the [alpha]3 integrin gene. For example, the expression of laminin in the basal lamina was greatly diminished, while there was a tremendous increase in the expression of fibronectin throughout the gland. This suggested that [alpha]3[Beta]1 integrin functions in the organization of laminin in the basal lamina while repressing expression of fibronectin. During SMG development, maturation of salivary epithelial depends, in part, on the interactions between laminin in the basement membrane and its integrin receptor, [alpha]3[Beta]1. It will be shown that filamentous actin (F-actin)appeared polarized to apical regions of differentiating acinar and ducial cells of the SMG. In the absence of [alpha]3[Beta]1 integrin, apical F-actin was decreased, which was accompanied by an apparent increase in F-actin at basal and lateral cell interfaces. Changes in the distribution of F-actin were accompanied by changes in cell shape, a consequence of an apparent decrease in cell polarity. In the absence of [alpha]3 integrin, embryonic day 18 (E18) mouse SMGs had defects in the basement membrane and in the apical basal polarity axis, as well as altered expression and/or localization of several ECM, adhesive and signaling molecule. In particular, there was a notable increase in the E-cadherin reactivity in the mutant SMGs and an apparent greater compaction of the gland. In addition, there was a decrease in P-cadherin reactivity in the mutant SMGs compared to the wild type. Here, it was examined whether altered E-cadherin immunostaining correlated with changes in salivary cell proliferation and apoptosis. Immunostaining for Proliferating Cell Nuclear Antigen (PCNA) in frozen E18 SMG sections from wild type and [alpha]3-knockout mice revealed a higher number of proliferative cells in the mutant. Furthermore, analyses of immunoreactivity of parotid secretory protein (PSP), a proacinar cell marker, and N-acetylglucosamine-1-P transferase (GPT), an in vivo marker for salivary cell proliferation, also showed an increased overall staining in the mutant glands. This was accompanied by a decrease in apoptosis in the mutant gland, as judged by Apostain reactivity. It was concluded that [alpha]3[Beta]1 integrin serves a critical role in the assembly of both the actin cytoskeleton and the ECM in the developing SMG. [alpha]3 integrin-deficient SMGs display changes in the balance between proliferation and apoptosis, a likely consequence of multiple changes in the expression and localization of adhesive and signaling molecules in the mutant tissue.
PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact firstname.lastname@example.org.Thesis (M.S.D.)--Boston University, Henry M. Goldman School of Dental Medicine, 2002 (Orthodontics).Includes bibliographical references (leaves 39-41).
RightsThis work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact email@example.com.