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PMID: 7559778 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of cell biology ·Vol. 131 ·No. 1 ·1995-10-00 ·Pages 215-26

Yang Y, Spitzer E, Meyer D, Sachs M, Niemann C, Hartmann G, Weidner KM, Birchmeier C, 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.

MeSH Terms
Animals Base Sequence Cell Differentiation/physiology Epithelial Cells Female Gene Expression Regulation, Developmental/physiology Glycoproteins/physiology Hepatocyte Growth Factor/physiology In Situ Hybridization Mammary Glands, Animal/cytology,embryology Mice Mice, Inbred BALB C Molecular Sequence Data Morphogenesis/physiology Neuregulins Oligonucleotides, Antisense/pharmacology Organ Culture Techniques
Chemicals
Glycoproteins Neuregulins Oligonucleotides, Antisense Hepatocyte Growth Factor
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Yang Y
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Spitzer E
Meyer D
Sachs M
Niemann C
Hartmann G
Weidner K M
Birchmeier C
Birchmeier W
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.131.1.215
Published
1995-10-00
Pages
215-26
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120590
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.131.1.215 PMC Full Text View journal details
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