Macrophage-stimulating protein and calcium homeostasis in zebrafish

作者：Huitema Leonie F A; Renn Joerg; Logister Ive; Gray Jerilyn K; Waltz Susan E; Flik Gert; Schulte Merker Stefan^*

来源：The FASEB Journal, 2012, 26(10): 4092-4101.

DOI：10.1096/fj.11-202663

• msp
• ron
• mineralization
• bone
• osteogenesis
• stanniocalcin

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

• 出版日期2012-10