Dynamic Assembly of Basement Membrane Components in Tissue Development during Pregnancy

Abstract

Extracellular matrix (ECM) functions as the insoluble scaffold of tissues that controls cellular behaviors and regulates environmental cues that are essential for many aspects of biology. Basement membranes (BMs) are specialized forms of ECM comprised of a collection of proteins, including collagen IV and laminin, which establish a sheet-like supramolecular arrangement. BMs create barriers between cell populations and modulate cellular crosstalk by underlying polarized cells of vascular, ductal, and glandular tissues and encasing essential cells of the reproductive, nervous, muscular systems and fat tissues. Recent discoveries suggest that BMs contribute to physiology and disease through dynamic regulation of BM composition and organization within tissues. Moreover, extracellular components peroxidasin and Goodpasture-antigen binding protein (GPBP) are emerging as members of the BM that have important roles in developmental and pathological process involving dynamic transitions of tissues. The works described in this dissertation addresses the dynamic interplay of BM components in pregnancy. We sought to test the hypothesis that BM structure and components are dynamically regulated during uterine, embryonic, and extraembryonic tissue development for pregnancy. Electron microscopy, polymerase chain reaction, and immunofluorescence revealed the novel finding that BM components have distinct and integrated patterns of localization in uterine tissues during decidualization. Findings from in utero and in vitro culture studies of early embryonic development suggested that specific BM components were utilized for early epithelial genesis. In extraembryonic tissues, BM components changed localization patterns throughout development. These findings advance fundamental knowledge about BM dynamics in pregnancy that translates to other cellular and molecular physiological and pathological processes, such as tissue morphogenesis and cancer.