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Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland

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Item Type:Article
Title:Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland
Creators Name:Yang, Y. and Spitzer, E. and Meyer, D. and Sachs, M. and Niemann, C. and Hartmann, G. and Weidner, K.M. and Birchmeier, C. and Birchmeier, W.
Abstract:We have examined the role of two mesenchymal ligands of epithelial tyrosine kinase receptors in mouse mammary gland morphogenesis. In organ cultures of mammary glands, hepatocyte growth factor (HGF, scatter factor) promoted branching of the ductal trees but inhibited the production of secretory proteins. Neuregulin (NRG, neu differentiation factor) stimulated lobulo-alveolar budding and the production of milk proteins. These functional effects are paralleled by the expression of the two factors in vivo: HGF is produced in mesenchymal cells during ductal branching in the virgin animal; NRG is expressed in the mesenchyme during lobulo-alveolar development at pregnancy. The receptors of HGF and NRG (c-met, c-erbB3, and c-erbB4), which are expressed in the epithelial cells, are not regulated. In organ culture, branching morphogenesis and lobulo-alveolar differentiation of the mammary gland could be abolished by blocking expression of endogenous HGF and NRG by the respective antisense oligonucleotides; in antisense oligonucleotide-treated glands, morphogenesis could again be induced by the addition of recombinant HGF and NRG. We thus show that two major postnatal morphogenic periods of mammary gland development are dependent on sequential mesenchymal-epithelial interactions mediated by HGF and NRG.
Keywords:Animal Mammary Glands, Antisense Oligonucleotides, Base Sequence, Cell Differentiation, Developmental Gene Expression Regulation, Epithelial Cells, Glycoproteins, Hepatocyte Growth Factor, In Situ Hybridization, Molecular Sequence Data, Morphogenesis, Neuregulins, Organ Culture Techniques, Animals, Mice
Source:Journal of Cell Biology
ISSN:0021-9525
Publisher:Rockefeller University Press (U.S.A.)
Volume:131
Number:1
Page Range:215-226
Date:October 1995
Additional Information:Copyright (c) 1995 by The Rockefeller University Press
Official Publication:http://www.jcb.org/cgi/content/abstract/131/1/215
PubMed:View item in PubMed

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