INVESTIGATING THE MORPHOGENESIS AND THE DYNAMICS OF HEPATIC INTERCELLULAR TISSUE STRUCTURES

Abstract

BILE CANALICULI NETWORK IS THE STRUCTURAL BASIS FOR LIVER TO ELIMINATE METABOLIC WASTES AND TOXINS. HOWEVER, LITTLE IS KNOWN ABOUT HOW THIS EPITHELIAL SECRETORY LUMEN GROWS AND DEVELOPS INTO A TUBULAR SHAPE. USING LIVE IMAGING, WE MONITORED DYNAMICS OF ACTOMYOSIN CONTRACTILITY AND BILE SECRETION DURING CANALICULI GROWTH. WE REVEALED THAT BILE SECRETION WAS THE DRIVING FORCE OF CANALICULI GROWTH WHEREAS ACTOMYOSIN CONTRACTILITY RESPONDED TO CANALICULI EXPANSION AND TRIGGERED CANALICULI CONTRACTIONS. TO INVESTIGATE ANISOTROPIC CANALICULI MORPHOGENESIS, WE CREATED A MICROWELL SYSTEM TO CONTROL 3D EXTRACELLULAR MATRIX (ECM) ORGANIZATION IN A DEFINED MICROENVIRONMENT. IT IS FOUND THAT ECM ADHESIONS COULD DIRECT CANALICULI ELONGATION VIA MODULATING INTERCELLULAR STRESS. WE DEMONSTRATED THAT CANALICULI PREFERRED TO ELONGATE TOWARDS THE WEAKER REGIONS WITHIN CELL-CELL CONTACTS, WHICH WERE REGULATED BY THE STRENGTH OF THE UNDERLYING CELL-ECM ADHESIONS.THEREFORE WE ELUCIDATED NOVEL MECHANISMS RE