Document Detail

ErbB4 modulates tubular cell polarity and lumen diameter during kidney development.
MedLine Citation:
PMID:  22076439     Owner:  NLM     Status:  MEDLINE    
ErbB4 receptor tyrosine kinase contributes to the development of the heart, the central nervous system, and the lactating mammary gland, but whether it has a role in the development of the kidney epithelium is unknown. Here, we found that expression of Erbb4 isoforms JM-a CYT-1 and JM-a CYT-2 was first detectable around embryonic day 13 in the mouse, mainly in the collecting ducts and both the proximal and distal tubules. In vitro, overexpression of a relevant ErbB4 isoform promoted proliferation and disturbed polarization of kidney epithelial cells when cultured as three-dimensional structures. We examined ErbB4 function in developing kidney tubules in vivo with Pax8-Cre-mediated conditional overexpression of Rosa26 locus-targeted ERBB4 and with conditional Erbb4 knock-out mice. The Pax8-Cre-driven ERBB4 overexpression enhanced proliferation in the collecting ducts, reduced the size of epithelial duct lumens, and promoted formation of cortical tubular cysts. These defects were associated with changes in the subcellular distribution of markers of epithelial cell polarity. Similarly, the Pax8-Cre-mediated Erbb4 knock-out mice manifested dysfunctional kidneys with larger duct lumens and epithelial cell mispolarization. Taken together, these data suggest that ErbB4 signaling modulates proliferation and polarization, cellular functions critical for the development of epithelial ducts in the kidney.
Ville Veikkolainen; Florence Naillat; Antti Railo; Lijun Chi; Aki Manninen; Peter Hohenstein; Nick Hastie; Seppo Vainio; Klaus Elenius
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-11-10
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  23     ISSN:  1533-3450     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-09     Completed Date:  2012-03-09     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  112-22     Citation Subset:  IM    
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MeSH Terms
Cell Polarity*
Cell Proliferation
Epithelial Cells / physiology
Isoenzymes / metabolism
Kidney Tubules / cytology,  embryology*,  metabolism
Mice, Inbred C57BL
Mice, Knockout
Receptor, Epidermal Growth Factor / genetics,  metabolism*
Grant Support
MC_U127527180//Medical Research Council
Reg. No./Substance:
0/Isoenzymes; EC, Epidermal Growth Factor; EC tyrosine-protein kinase erbB-4
Comment In:
J Am Soc Nephrol. 2012 Jan;23(1):4-5   [PMID:  22158432 ]

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