A. Chausovsky et al., MORPHOGENETIC EFFECTS OF NEUREGULIN (NEU DIFFERENTIATION FACTOR) IN CULTURED EPITHELIAL-CELLS, Molecular biology of the cell, 9(11), 1998, pp. 3195-3209
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 indu
ce profound morphogenic responses in cultured epithelial cells of diff
erent origins. These effects include scattering of small epithelial is
lands and rearrangement of larger cell islands into ordered ring-shape
d arrays with internal lumens. The ring-forming cells are interconnect
ed by cadherin- and beta-catenin-containing adherens junctions. In con
fluent cultures, neuregulin treatment induces formation of circular lu
menlike gaps in the monolayer. Both cell scattering and ring formation
are accompanied by a marked increase in cell motility that is indepen
dent of hepatocyte growth factor/scatter factor and its receptor (c-Me
t). 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 ne
uregulin.