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Gli是一种锌指转录因子和癌基因,在正常小鼠发育过程中表达。

gli, a zinc finger transcription factor and oncogene, is expressed during normal mouse development.

作者信息

Walterhouse D, Ahmed M, Slusarski D, Kalamaras J, Boucher D, Holmgren R, Iannaccone P

机构信息

Department of Pediatrics, Northwestern University, Chicago, Illinois 60611.

出版信息

Dev Dyn. 1993 Feb;196(2):91-102. doi: 10.1002/aja.1001960203.

Abstract

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 (ciD), 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 cephalopolysyndactylyl 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.

摘要

致癌基因GLI在一些人类恶性胶质瘤和儿童未分化肉瘤病例中被扩增和表达,它是一个基因家族的原型,其特征是有一组高度保守的五个串联锌指结构和一个共有半胱氨酸 - 组氨酸连接。已证明这种锌指基序能以序列特异性结合DNA,并可能介导转录调控。由于GLI在胚胎癌细胞系中表达,但在大多数正常成年组织中不表达,并且在其锌指结构域内与果蝇分割基因“间断翅脉显性(ciD)”有显著的序列相似性,已知ciD在每个幼虫节段后部的形态发生中很重要,我们用Northern印迹法、逆转录酶联PCR和原位杂交技术确定了人GLI的小鼠同源物在第10至18天小鼠胚胎中的时空表达模式。在小鼠胚胎发育的第10至18天以及正常成年子宫、脑、睾丸和肢体中都检测到了gli转录本。在妊娠期间,gli在梅克尔软骨前间充质、枕基部、肋骨间充质凝聚物、原始椎体、前足和后足板中的指状间充质凝聚物、脊髓室管膜层以及胃肠道中胚层中都有表达。在四肢、肋骨和椎体以及胃肠道中胚层的发育中的骨骼和软骨中,表达在整个妊娠期间持续存在。这些发现支持了gli家族基因在哺乳动物正常颅面和指发育中的作用,这一作用最早是通过在患有Greig头多指综合征的家族中GLI3基因内易位断点的证明,以及随后在小鼠突变体extra toes中gli3表达降低而提出的。令人惊讶的是,一个单一基因会在如此广泛的间充质结构中表达。

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