Abstract: Series 105, Lecture 1

The Harvey Lectures Series 105 (2009—2010)

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Lecture #1: Thursday, October 8, 2009 — Time and Location

Terminal Differentiation of Epithelial Cells

Qais Al-Awqati, MB, ChB

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

Dr Al-Awqati's Website

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.