Holzenberger M, Lapointe F, Leibovici M, Lièvre C A
Institut d'Embryologie Cellulaire et Moléculaire, CNRS, Nogent-sur-Marne, France.
Brain Res Dev Brain Res. 1996 Nov 22;97(1):76-87. doi: 10.1016/s0165-3806(96)00133-2.
Insulin-like growth factor type 1 receptor (IGF-1R) is a tyrosine kinase with a key role in development. The primary structure of IGF-1R is known for mammalian species, but not for birds. The avian embryo, however, provides an ideal system for the experimental study of neurogenesis. We therefore cloned the complete coding sequence of the chicken IGF-1R from a cDNA library and analyzed its embryonic expression by Northern blot and in situ hybridization. The deduced chicken IGF-1R precursor of 1363 amino acids was 85% identical to human IGF-1R and did not show deletions or insertions in critical positions, when compared to its mammalian homologues. Notably, all cysteine residues in the extracellular domains, and 15 of the 17 N-linked glycosylation sites found in human IGF-1R were also present in the chicken receptor. An 11 kb transcript was abundant in developing nervous tissues, kidney, pancreas and the gastrointestinal tract. The early in situ expression patterns in 20-somite embryos revealed high levels of IGF-1R mRNA in the neuroepithelia, notochord and somites. At embryonic day 4 (E4), high concentrations of IGF-1R transcripts were found again primarily in the neuroepithelia and, to a lesser degree, in the sensory ganglia and diverse mesenchymal derivatives. During the second half of embryonic development, IGF-1R expression in the CNS was particularly abundant in telencephalic regions, including the olfactory bulb, hippocampus, striatum and piriform cortex, and also in the optic tectum and cerebellum. By the use of cDNA cloning and in situ hybridization this study reveals conserved amino acid sequence elements between birds and mammals, and developmental expression patterns that are compatible with an important role of this receptor in growth, differentiation and maturation of the avian CNS.
胰岛素样生长因子1型受体(IGF-1R)是一种在发育过程中起关键作用的酪氨酸激酶。IGF-1R的一级结构在哺乳动物物种中是已知的,但在鸟类中尚不清楚。然而,禽类胚胎为神经发生的实验研究提供了一个理想的系统。因此,我们从cDNA文库中克隆了鸡IGF-1R的完整编码序列,并通过Northern印迹和原位杂交分析了其胚胎表达。推导的鸡IGF-1R前体由1363个氨基酸组成,与人类IGF-1R的同源性为85%,与哺乳动物同源物相比,在关键位置没有缺失或插入。值得注意的是,鸡受体的细胞外结构域中的所有半胱氨酸残基以及人类IGF-1R中发现的17个N-连接糖基化位点中的15个也存在。一个11 kb的转录本在发育中的神经组织、肾脏、胰腺和胃肠道中丰富表达。20体节胚胎的早期原位表达模式显示,神经上皮、脊索和体节中IGF-1R mRNA水平较高。在胚胎第4天(E4),再次发现高浓度的IGF-1R转录本主要存在于神经上皮中,其次是感觉神经节和各种间充质衍生物。在胚胎发育的后半期,IGF-1R在中枢神经系统中的表达在端脑区域特别丰富,包括嗅球、海马、纹状体和梨状皮质,也在视顶盖和小脑中表达。通过使用cDNA克隆和原位杂交,本研究揭示了鸟类和哺乳动物之间保守的氨基酸序列元件,以及与该受体在禽类中枢神经系统的生长、分化和成熟中的重要作用相一致的发育表达模式。