ZFIN ID: ZDB-PUB-120718-23
Macrophage-stimulating protein and calcium homeostasis in zebrafish
Huitema, L.F., Renn, J., Logister, I., Gray, J.K., Waltz, S.E., Flik, G., and Schulte-Merker, S.
Date: 2012
Source: FASEB journal : official publication of the Federation of American Societies for Experimental Biology   26(10): 4092-4101 (Journal)
Registered Authors: Flik, Gert, Huitema, Leonie, Logister, Ive, Renn, Joerg, Schulte-Merker, Stefan
Keywords: msp, ron, mineralization, bone, osteogenesis, stanniocalcin
MeSH Terms:
  • Animals
  • Calcium/metabolism*
  • Glycoproteins/metabolism
  • Hepatocyte Growth Factor/genetics
  • Hepatocyte Growth Factor/metabolism*
  • Homeostasis/genetics
  • Homeostasis/physiology
  • Osteogenesis/genetics
  • Osteogenesis/physiology
  • Proto-Oncogene Proteins/genetics
  • Proto-Oncogene Proteins/metabolism*
  • Receptor Protein-Tyrosine Kinases/genetics
  • Receptor Protein-Tyrosine Kinases/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 22787265 Full text @ FASEB J.

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.