IGFBP5 is a potential regulator of craniofacial skeletogenesise

Six known proteins bind to the insulin-like growth factor (IGF) with high affinity. lgfbp5 encodes one of these proteins, which regulates the activity of IGF, but also exerts IGF-independent actions. Using in situ hybridization to detect cells expressing lgfbp5 mRNA, we show that lgfbp5 is expressed in a dynamic pattern in the mouse embryonic craniofacial region. At early stages corresponding to the completion of neural crest migration, lgfbp5 mRNA was found predominantly in the epithelia, whereas when the craniofacial mesenchyme has begun its differentiation into skeletal tissue, lgfbp5-expressing cells surrounded the developing cartilages and bones. Embryos transgenically expressing lgfbp5 in restricted areas of the mesenchyme fated to form craniofacial bones revealed decreased ossification and even deletion of head bones areas. Transgenic expression of a mutant lgfbp5, encoding a product with reduced binding affinity for IGF, led to no skeletal abnormalities, suggesting that the observed negative effects on skeletal development rely on a mechanism that depends on binding to IGF.