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Vol. 9, Issue 11, 3195-3209, November 1998

Morphogenetic Effects of Neuregulin (Neu Differentiation Factor) in Cultured Epithelial Cells

Alexander Chausovsky,* Ilan Tsarfaty,dagger Zvi Kam,* Yosef Yarden,Dagger Benjamin Geiger,* and Alexander D. Bershadsky*§

Departments of  *Molecular Cell Biology and  Dagger Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel; and  dagger Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel

Neuregulin, or neu differentiation factor, induces cell proliferation or differentiation through interaction with members of the ErbB family of receptor tyrosine kinases. We report that neuregulin can also induce profound morphogenic responses in cultured epithelial cells of different origins. These effects include scattering of small epithelial islands and rearrangement of larger cell islands into ordered ring-shaped arrays with internal lumens. The ring-forming cells are interconnected by cadherin- and beta -catenin-containing adherens junctions. In confluent cultures, neuregulin treatment induces formation of circular lumenlike gaps in the monolayer. Both cell scattering and ring formation are accompanied by a marked increase in cell motility that is independent of hepatocyte growth factor/scatter factor and its receptor (c-Met). Affinity-labeling experiments implied that a combination of ErbB-2 with ErbB-3 mediates the morphogenic signal of neuregulin in gastric cells. Indeed, a similar morphogenic effect could be reconstituted in nonresponsive cells by coexpression of ErbB-2 and -3. We conclude that a heterodimer between the kinase-defective neuregulin receptor, ErbB-3, and the coreceptor, ErbB-2, mediates the morphogenetic action of neuregulin.

§   Corresponding author. E-mail address: libersha{at}weizmann.weizmann.ac.il.

Molecular Biology of the Cell
Vol. 9, 3195-3209, November 1998
Copyright © 1998 by The American Society for Cell Biology


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