GLI, A ZINC-FINGER TRANSCRIPTION FACTOR AND ONCOGENE, IS EXPRESSED DURING NORMAL MOUSE DEVELOPMENT
GLI, A ZINC-FINGER TRANSCRIPTION FACTOR AND ONCOGENE, IS EXPRESSED DURING NORMAL MOUSE DEVELOPMENT
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DOI：
10.1002/aja.1001960203
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发表时间：
1993-02-01
影响因子：
2.5
通讯作者：
IANNACCONE, P
中科院分区：
文献类型：
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作者：
WALTERHOUSE, D;AHMED, M;IANNACCONE, P
癌基因GLI在一些人类恶性胶质瘤和未分化的儿童肉瘤中扩增和表达，是一个基因家族的原型，该基因家族具有高度保守的五个串联锌指和一致的半胱氨酸-组氨酸连接。这个锌指基序已被证明与DNA结合具有序列特异性，并可能介导转录调控。由于GLI在胚胎癌细胞系中表达，但在大多数正常成人组织中不表达，并且在其锌指域内与果蝇片段基因Ci(D)具有显著的序列相似性，Ci(D)是已知在每个幼虫节段的后部形态发生中起重要作用的基因。我们通过Northern印迹、逆转录酶偶联聚合酶链式反应和原位杂交，建立了人GLI同源物在第10天到18天小鼠胚胎中的时间和组织表达模式。在小鼠胚胎发育的第10天到第18天，以及在正常的成年子宫、脑、睾丸和四肢中都发现了Gli的转录本。Meckel‘s软骨前间充质、枕骨、肋间充质、原始椎体、前足板和后足板的指间质、脊髓室管膜层和胃肠道中胚层均有GliI的组织表达。在整个妊娠期间，在四肢、肋骨和椎体以及胃肠道中胚层的骨骼和软骨的发育中持续表达。这些发现支持GLI家族基因在哺乳动物正常的头面部和手指发育中的作用，首先是在Greig头多指综合征家族中GLI3基因内的易位断裂点的证明，随后是通过突变的小鼠额外脚趾中GLI3表达的减少而提出的。令人惊讶的是，单个基因会在如此广泛的间质结构中表达。(C)1993年Wiley-Liss，Inc.
The oncogene GLI is amplified and expressed in some cases of human malignant glioma and undifferentiated childhood sarcoma and is the prototype for a gene family characterized by a highly conserved set of five tandem zinc fingers and a consensus cysteine-histidine link. This zinc finger motif has been shown to bind DNA with sequence specificity and may mediate transcriptional regulation. Since GLI is expressed in embryonal carcinoma cell lines but not in most normal adult tissues and shows significant sequence similarity within its zinc finger domain to cubitus interruptus dominant (ci(D)), a Drosophila segmentation gene known to be important in the morphogenesis of the posterior portion of each larval segment, we established the temporal and tissue expression patterns of the mouse homologue of human GLI in day 10 through 18 mouse embryos with Northern blotting, reverse transcriptase coupled PCR, and in situ hybridization. gli transcripts were demonstrated on days 10 through 18 of mouse embryonic development as well as in normal adult uterus, brain, testis, and limb. Tissue expression of gli during gestation was demonstrated in Meckel's precartilage mesenchyme, the basis occipitus, rib mesenchymal condensations, primordial vertebral bodies, digital mesenchymal condensations in forefoot and hindfoot plates, the ependymal layer of the spinal cord, and the mesoderm of the gastrointestinal tract. Expression persisted throughout gestation in developing bone and cartilage of the extremities, the ribs, and the vertebral bodies, as well as the gastrointestinal tract mesoderm. These findings support a role for gli family genes in normal craniofacial and digital development in mammals first suggested by the demonstration of translocation breakpoints within the GLI3 gene in families with the Greig cephalopolysyndactyly syndrome and subsequently by reduced gli3 expression in the mouse mutant extra toes. It is surprising that a single gene would be expressed in such a wide range of mesenchymal structures. (C) 1993 Wiley-Liss, Inc.