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Macrophage‐stimulating protein and calcium homeostasis in zebrafish
Author(s) -
Huitema Leonie F. A.,
Renn Jörg,
Logister Ive,
Gray Jerilyn K.,
Waltz Susan E.,
Flik Gert,
SchulteMerker Stefan
Publication year - 2012
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/fj.11-202663
Subject(s) - zebrafish , mutant , microbiology and biotechnology , gene knockdown , biology , calcium metabolism , calcium , transgene , positional cloning , phenotype , homeostasis , mutagenesis , gene , genetics , chemistry , organic chemistry
To systematically identify novel gene functions essential for osteogenesis and skeletal mineralization, we performed a forward genetic mutagenesis screen in zebrafish and isolated a mutant that showed delayed skeletal mineralization. Analysis of the mutant phenotype in an osterix :nuclear‐GFP transgenic background demonstrated that mutants contain osterix ‐expressing osteoblasts comparable to wild‐type embryos. Positional cloning revealed a premature stop mutation in the macrophage‐stimulating protein ( msp ) gene, predicted to result in a biologically inactive protein. Analysis of the embryonic expression pattern for the receptor for Msp, Ron, shows specific expression in the corpuscles of Stannius, a teleost‐specific organ that produces stanniocalcin, a pivotal hormone in fish calcium homeostasis. Knockdown of Ron resulted in identical phenotypes as observed in msp mutants. Msp mutant embryos could be rescued by excess calcium. Consistent with a role for Msp/Ron in calcium homeostasis, calcium‐regulating factors, such as pth1, pth2, stc1l , and trpv5/6 were significantly affected in msp mutant larvae. While Msp and Ron have previously been shown to play a critical role in a wide variety of biological processes, we introduce here the Msp/Ron signaling axis as a previously unappreciated player in calcium homeostasis and embryonic skeletal mineralization.—Huitema, L. F. A., Renn, J., Logister, I., Gray, J. K., Waltz, S. E., Flik, G., Schulte‐Merker, S. Macrophage stimulating protein and calcium homeostasis in zebrafish. FASEB J. 26, 4092–4101 (2012). www.fasebj.org