The N-myc proto-oncogene and IGF-II growth factor mRNAs are expressed by distinct cells in human fetal kidney and brain.

The N-myc proto-oncogene and IGF-II growth factor mRNAs are expressed by distinct cells in human fetal kidney and brain.
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DOI:
10.1083/jcb.108.3.1093
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发表时间:
1989-03
影响因子:
7.8
通讯作者:
Alitalo, K
Alitalo, K
中科院分区:
生物学1区
文献类型:
--
作者:
Hirvonen, H;Sandberg, M;Kalimo, H;Hukkanen, V;Vuorio, E;Salmi, T T;Alitalo, K

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我们研究了N-myc原癌基因和胰岛素样生长因子-II(IGF-II)基因在16-19孕周胎儿中的表达。这两个基因在胚胎组织的生长和分化中都有特定的作用,如肾脏和神经组织。由于N-myc和IGF-II mRNAs的持续表达也是肾母细胞瘤的一个特征,这是一种可能起源于胎儿肾脏的儿童肿瘤,我们特别感兴趣的是它们在发育中的肾脏中表达可能是连锁的或协调调节的。Northern杂交结果显示,N-myc基因在脑和肾脏中均有表达。肾组织原位杂交显示,N-myc放射自显影颗粒主要位于上皮分化间充质细胞上方,而大多数间充质基质细胞与N-myc探针仅显示背景信号。N-myc mRNA在整个发育中的大脑中都能检测到,在室管膜下和皮质层之间的中间带细胞中略有增加。因此,即使是有丝分裂后的胎儿大脑神经上皮细胞也表达N-myc mRNA。在Northern杂交中,IGF-II的mRNA信号在肾脏中丰富,但在脑中虽然明确,但信号要弱得多。肾脏中IGF-II mRNA的区域分布与N-myc的分布具有很大的互补性。IGF-II放射自显影颗粒主要位于间质和胚泡细胞上,上皮结构上相对缺乏杂交。在大脑中,IGF-II在室管膜下层和中间层的含量分别是皮质板和室管膜区的两到三倍。N-myc和IGF-II在胎儿中的表达模式反映在已知的在出生后生活中表达相应基因的肿瘤类型上,如Wilms瘤。然而,IGF-II和N-myc基因在未成熟肾脏中的明显共表达主要发生在不同的细胞类型中。
We studied the expression of the N-myc proto-oncogene and the insulin- like growth factor-II (IGF-II) gene in human fetuses of 16-19 gestational wk. Both genes have specific roles in the growth and differentiation of embryonic tissues, such as the kidney and neural tissue. Since continued expression of N-myc and IGF-II mRNAs is also a characteristic feature of Wilms' tumor, a childhood neoplasm of probable fetal kidney origin, we were particularly interested in the possibility that their expression might be linked or coordinately regulated in the developing kidney. Expression of N-myc mRNA was observed in the brain and in the kidney by Northern hybridization analysis. In in situ hybridization of the kidney, N-myc autoradiographic grains were primarily located over epithelially differentiating mesenchyme while most of the mesenchymal stromal cells showed only a background signal with the N-myc probe. N-myc mRNA was detectable throughout the developing brain with a slight accentuation in the intermediate zone cells in between the subependymal and cortical layers. Thus, even postmitotic neuroepithelial cells of the fetal cerebrum expressed N-myc mRNA. In Northern hybridization, IGF-II mRNA signal was abundant in the kidney but much weaker, though definite, in the brain. The regional distribution of IGF-II mRNA in the kidney was largely complementary to that of N-myc. IGF-II autoradiographic grains were located predominantly over the stromal and blastemal cells with a relative lack of hybridization over the epithelial structures. In the brain, IGF-II mRNA was about two- to threefold more abundant in the subependymal and intermediate layers than in the cortical plate and ependymal zone, respectively. The fetal expression patterns of the N- myc and IGF-II mRNAs are reflected by the types of tumors known to express the corresponding genes during postnatal life such as Wilms' tumor. However, the apparent coexpression of the IGF-II and N-myc genes in immature kidneys occurs largely in distinct cell types.