Bobola Nicoletta, Engist Bettina
Department of Developmental Biology, Max-Planck Institute of Immunobiology, Stuebeweg 51, D-79108, Freiburg, Germany.
Genesis. 2008 Jan;46(1):52-9. doi: 10.1002/dvg.20360.
Six known proteins bind to the insulin-like growth factor (IGF) with high affinity. Igfbp5 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 Igfbp5 mRNA, we show that Igfbp5 is expressed in a dynamic pattern in the mouse embryonic craniofacial region. At early stages corresponding to the completion of neural crest migration, Igfbp5 mRNA was found predominantly in the epithelia, whereas when the craniofacial mesenchyme has begun its differentiation into skeletal tissue, Igfbp5-expressing cells surrounded the developing cartilages and bones. Embryos transgenically expressing Igfbp5 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 Igfbp5, 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.
六种已知蛋白质能与胰岛素样生长因子（IGF）高亲和力结合。Igfbp5编码其中一种蛋白质，该蛋白质不仅调节IGF的活性，还发挥不依赖IGF的作用。通过原位杂交检测表达Igfbp5 mRNA的细胞，我们发现Igfbp5在小鼠胚胎颅面区域以动态模式表达。在对应神经嵴迁移完成的早期阶段，Igfbp5 mRNA主要存在于上皮细胞中，而当颅面间充质开始分化为骨骼组织时，表达Igfbp5的细胞围绕着发育中的软骨和骨骼。在注定形成颅面骨的间充质受限区域转基因表达Igfbp5的胚胎显示骨化减少，甚至头部骨骼区域缺失。编码与IGF结合亲和力降低的产物的突变型Igfbp5的转基因表达未导致骨骼异常，这表明观察到的对骨骼发育的负面影响依赖于一种依赖于与IGF结合的机制。
