Abstract: Series 105, Lecture 1
The Harvey Lectures Series 105 (2009—2010)
Lecture #1: Thursday, October 8, 2009 — Time and Location
Terminal Differentiation of Epithelial Cells
Qais Al-Awqati, MB, ChB
Robert F Loeb Professor of Medicine
Department of Medicine
College of Physicians and Surgeons, Columbia University
New York, New York
All embryonic epithelial cells first appear to be flat with few apical features; then a signal induces them to assume their final shape be it simple columnar cells or a multi-layered epithelium. We identified a new program that converts a featureless flat cell in the kidney to a columnar cell with mature apical microvilli and apical endocytosis. This conversion begins when the differentiation signal causes a new monomeric extracellular protein which we termed hensin to polymerize and be deposited in the ECM. Polymerization of hensin requires activation of ß1-integrin and secretion of two small proteins galectin3 and a cis-trans prolyl isomerase. The polymeric extracellular hensin instructs the cell to maintain a memory of the signal as long as it is present in the ECM.