Extensive elongation of lens fiber cells is a central feature of lens morphogenesis. Our study investigates the role of N-cadherin junctions in this process in vivo. We investigate both the molecular players involved in N-cadherin junctional maturation and the subsequent function of these junctions as epicenters for the assembly of an actin cytoskeleton that drives morphogenesis. We present the first evidence of nascent cadherin junctions in vivo, and show they are a prominent feature along lateral interfaces of undifferentiated lens epithelial cells. Maturation of these N-cadherin junctions, required for lens cell differentiation, preceded organization of a cortical actin cytoskeleton along the cells’ lateral borders, but was linked to recruitment of α-catenin and dephosphorylation of N-cadherin-linked β-catenin. Biochemical analysis revealed differentiation-specific recruitment of actin regulators cortactin and Arp3 to maturing N-cadherin junctions of differentiating cells, linking N-cadherin junctional maturation with actin cytoskeletal assembly during fiber cell elongation. Blocking formation of mature N-cadherin junctions led to reduced association of α-catenin with N-cadherin, prevented organization of actin along lateral borders of differentiating lens fiber cells and blocked their elongation. These studies provide a molecular link between N-cadherin junctions and the organization of an actin cytoskeleton that governs lens fiber cell morphogenesis in vivo.

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Our previous studies of brain tissues obtained at autopsy have established an association of Chlamydia pneumoniae (Cpn) infection with late‐onset Alzheimer’s disease (AD). Given these findings, we have designed a study using electron microscopy (EM) to determine if various forms of Cpn from geriatric patient’s blood samples could be identified and correlated with cognitive decline associated with AD. Patients, >65 years old, and who participated in this IRB approved study, met well‐defined exclusion criteria prior to being evaluated for cognitive status using the SLUMS and FAST testing assessments. After psychometric testing, blood was drawn from the patients and these samples were prepared for EM and assessed for the presence of Cpn. Our ultrastructural analysis revealed evidence for the presence of Cpn in peripheral blood cells from 12 patients correlated with MCI and AD. Intravacuolar reticulate bodies, elementary bodies, and intermediate bodies characteristic of Cpn were observed in leukocytes from the buffy coat. More specifically, we observed the classical “pear‐shaped” elementary bodies characteristic of Cpn. Immuno‐ EM was performed for positive identification of these various forms of Cpn. Our data indicate that screening for Cpn from blood samples may prove to be a viable biomarker in differentiating cognitive change consistent with stages associated with MCI and AD. Investigating the distinct morphologies of Cpn in human blood samples from the geriatric population by EM, with other frontline diagnostic procedures, may clarify the diagnosis of MCI and late onset AD. Grant Funding Source: Center for Chronic Disorders of Aging