ZFIN ID: ZDB-PUB-041122-6
Insulin-like Growth Factor-binding Protein-3 Plays an Important Role in Regulating Pharyngeal Skeleton and Inner Ear Formation and Differentiation
Li, Y., Xiang, J., and Duan, C.
Date: 2005
Source: The Journal of biological chemistry   280(5): 3613-3620 (Journal)
Registered Authors: Duan, Cunming
Keywords: none
MeSH Terms:
  • Animals
  • Cartilage/embryology
  • Cartilage/metabolism
  • Ear, Inner/embryology*
  • Ear, Inner/metabolism*
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins/genetics
  • Insulin-Like Growth Factor Binding Protein 3/genetics
  • Insulin-Like Growth Factor Binding Protein 3/metabolism*
  • Mutagenesis
  • Pharynx/embryology*
  • Pharynx/metabolism*
  • RNA, Messenger/metabolism
  • Zebrafish
PubMed: 15550380 Full text @ J. Biol. Chem.
Insulin-like growth factor binding protein (IGFBP)-3 is the major IGF carrier protein in the bloodstream. IGFBP-3 prolongs the half-life of circulating IGFs and prevents their potential hypoglycemic effect. IGFBP-3 is also expressed in many peripheral tissues in fetal and adult stages. In vitro, IGFBP-3 can inhibit or potentiate IGF actions, and even possesses IGF-independent activities, suggesting that local IGFBP-3 may also have paracrine/autocrine function(s). The in vivo function of IGFBP-3, however, is unclear. In this study, we elucidate the developmental role of IGFBP-3 using the zebrafish model. IGFBP-3 mRNA expression is first detected in the migrating cranial neural crest cells and subsequently in pharyngeal arches in zebrafish embryos. IGFBP-3 mRNA is also persistently expressed in the developing inner ears. To determine the role of IGFBP-3 in these tissues, we ablated the IGFBP-3 gene product using morpholino-modified antisense oligonucleotides (MOs). The IGFBP-3 knocked-down embryos had delayed pharyngeal skeleton morphogenesis and greatly reduced pharyngeal cartilage differentiation. Knockdown of IGFBP-3 also significantly decreased inner ear size and disrupted hair cell differentiation and semicircular canal formation. Furthermore, re-introduction of a MO-resistant form of IGFBP-3 "rescued" the MO-induced defects. These findings suggest that IGFBP-3 plays an important role in regulating pharyngeal cartilage and inner ear development and growth in zebrafish.