Macrophage-stimulating protein and calcium homeostasis in zebrafish

L.F.A. Huitema, J. Renn, I. Logister, J.K. Gray, S.E. Waltz, G. Flik, S. Schulte-Merker

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)4092-4101
JournalFASEB Journal
Volume26
Issue number10
DOIs
Publication statusPublished - 2012

Keywords

  • receptor tyrosine kinase
  • bone-resorption
  • gene-product
  • danio-rerio
  • growth
  • expression
  • identification
  • osteoblasts
  • activation
  • fish

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