Bondy C A, Werner H, Roberts C T, LeRoith D
Developmental Endocrinology Branch, National Institute of Child Health, National Institutes of Health, Bethesda, Maryland 20892.
Mol Endocrinol. 1990 Sep;4(9):1386-98. doi: 10.1210/mend-4-9-1386.
To investigate the potential role(s) of the insulin-like growth factors (IGFs) in embryogenesis, we have used in situ hybridization histochemistry to localize mRNAs for IGF-I, IGF-II, and the type I IGF receptor during an early period in rat embryonic development (embryonic days 14 and 15). IGF-I and IGF-II mRNAs were found in distinctly different patterns of cellular distribution. IGF-I mRNA was particularly abundant in undifferentiated mesenchymal tissue in the vicinity of sprouting nerves and spinal ganglia, and in circumscribed regions of the developing face that corresponded to the target zones of the trigeminal nerve. IGF-I mRNA was also found in aggregations of mesenchyme surrounding, but not in developing muscle and cartilage. IGF-I mRNA was selectively concentrated in areas of active tissue remodeling, such as the cardiac outflow tract, and was undetectable in liver, pituitary, and nervous system at this early stage of organogenesis. IGF-II mRNA was abundant in developing muscle, cartilage, and vascular tissue, and in the embryonic liver and pituitary. IGF-II mRNA was also conspicuous in areas of vascular interface with the brain, such as the choroid plexus and the organum vasculosum of the lamina terminalis. Messenger RNA for the type I IGF receptor was widely distributed in embryonic tissues, but the highest level were seen in the ventral floorplate of the hindbrain, where specialized neuroepithelial cells act as guides for axonal targeting. In conclusion, the different cellular patterns of expression of genes for IGF-I and IGF-II indicate that these two IGFs are differently regulated and, thus, may have significantly different roles in the process of embryonic development. Furthermore, the early and widespread expression of the type-I IGF receptor gene, in contrast to the relatively limited and localized pattern of IGF-I gene expression, is consistent with the view that this receptor may mediate the effects of IGF-II as well as IGF-I during embryogenesis.
为研究胰岛素样生长因子（IGFs）在胚胎发生中的潜在作用，我们采用原位杂交组织化学方法，在大鼠胚胎发育早期（胚胎第14和15天）定位IGF-I、IGF-II和I型IGF受体的mRNA。发现IGF-I和IGF-II mRNA的细胞分布模式明显不同。IGF-I mRNA在发芽神经和脊髓神经节附近的未分化间充质组织中特别丰富，并且在发育中面部与三叉神经靶区相对应的特定区域中也有发现。IGF-I mRNA也存在于围绕但不包括发育中的肌肉和软骨的间充质聚集体中。IGF-I mRNA选择性地集中在活跃的组织重塑区域，如心脏流出道，在器官发生的这个早期阶段，在肝脏、垂体和神经系统中未检测到。IGF-II mRNA在发育中的肌肉、软骨和血管组织以及胚胎肝脏和垂体中丰富。IGF-II mRNA在与脑的血管界面区域，如脉络丛和终板血管器中也很明显。I型IGF受体的信使RNA广泛分布于胚胎组织中，但在后脑腹侧底板中水平最高，在那里特殊的神经上皮细胞作为轴突靶向的引导。总之，IGF-I和IGF-II基因表达的不同细胞模式表明这两种IGF受到不同的调节，因此在胚胎发育过程中可能具有显著不同的作用。此外，与IGF-I基因表达相对有限和局部的模式相比，I型IGF受体基因早期广泛的表达与该受体可能在胚胎发生过程中介导IGF-II以及IGF-I的作用这一观点一致。
