PUBLICATION
Insulin-like Growth Factor-binding Protein-3 Plays an Important Role in Regulating Pharyngeal Skeleton and Inner Ear Formation and Differentiation
- Authors
- Li, Y., Xiang, J., and Duan, C.
- ID
- ZDB-PUB-041122-6
- 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.
Citation
Li, Y., Xiang, J., and Duan, C. (2005) Insulin-like Growth Factor-binding Protein-3 Plays an Important Role in Regulating Pharyngeal Skeleton and Inner Ear Formation and Differentiation. The Journal of biological chemistry. 280(5):3613-3620.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping