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Extracellular calcium regulates embryonic mouse lung function through the calcium‐sensing receptor
Author(s) -
Finney Brenda,
Moral Pierre M.,
Wilkinson William W.,
Cole Martin,
Martin David,
Warburton David,
Kemp Paul J.,
Riccardi Daniela
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.930.1
Subject(s) - extracellular , calcium , calcium sensing receptor , fetus , microbiology and biotechnology , lung , receptor , morphogenesis , in utero , embryonic stem cell , biology , calcium imaging , medicine , endocrinology , chemistry , calcium metabolism , biochemistry , pregnancy , gene , genetics
The widespread distribution of the extracellular calcium‐sensing receptor (CaR) and its sensitivity to acute physiologic changes in extracellular calcium concentration ([Ca 2+ ] o ) make it ideally suited to be a key regulator of Ca 2+ o ‐dependent cell fate during development. We investigated whether [Ca 2+ ] o , acting through the CaR, regulates murine lung development using embryonic day 12.5 lungs in whole organ culture. Ontogeny of CaR expression, determined using qPCR and immunohistochemistry, supported the use of this time point for experimentation. Branching morphogenesis and trans‐epithelial potential difference were exquisitely sensitive to changes in [Ca 2+ ] o . Branching morphogenesis was maximal between 1 and 1.2mM (adult level) and was maximally inhibited at 1.7mM [Ca 2+ ] o (fetal level). To probe the involvement of CaR in mediating the inhibitory effects of high [Ca 2+ ] o , we co‐treated cultured lungs with the CaR specific calcimimetic, AMG R‐568 (10nM) in the presence of 1.2mM [Ca 2+ ] o ; this suppressed lung branching rate to a level not significantly different from that at 1.7mM [Ca 2+ ] o . Together, our data suggest that fetal environmental Ca 2+ signals are important extrinsic factors that modulate the intrinsic lung developmental programme, and they strongly support a primary role for the CaR in preventing hyperplastic lung disease in utero . This project is supported by the BBSRC.