Orenic T V, Slusarski D C, Kroll K L, Holmgren R A
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208.
Genes Dev. 1990 Jun;4(6):1053-67. doi: 10.1101/gad.4.6.1053.
The segment polarity mutation, cubitus interruptus Dominant (ciD), of Drosophila melanogaster causes defects in the posterior half of every embryonic segment. We cloned sequences from the ciD region on the proximal fourth chromosome by "tagging" the gene with the transposable element P. Genetic and molecular evidence indicates that the P-element insertions, which all occurred within the same restriction fragment, are in 5'-regulatory regions of the ciD gene within 3 kb of the first exon of its transcript. The putative ciD transcript was identified on the basis of its absence in homozygous ciD embryos. Its spatial pattern of expression during development is unusual in that, unlike most other segmentation genes, it exhibits uniform expression throughout cellular blastoderm and gastrulation and does not resolve into a periodic pattern until the end of the fast phase of germ-band elongation when it is present in 15 broad segmentally repeating stripes along the anterior-posterior axis of the embryo. Registration of the ciD stripes of expression relative to the stripes of other segment polarity genes shows that ciD is expressed in the anterior three-quarters of every segment. This registration does not correlate with the pattern defects observed in ciD mutants. Sequence analysis indicates that the protein encoded by the ciD transcript contains a domain of five tandem amino acid repeats that have sequence similarity to the zinc-finger repeats of the Xenopus transcription factor TFIIIA and that share the highest degree of identity with the human zinc-finger protein GLI, which has been found to be amplified in several human glioblastomas.
果蝇黑腹果蝇的体节极性突变,即间断翅脉显性(ciD),会导致每个胚胎体节后半部分出现缺陷。我们通过用转座因子P “标记” 该基因,从近端第四条染色体上的ciD区域克隆了序列。遗传和分子证据表明,所有发生在同一限制性片段内的P因子插入,都位于ciD基因转录本第一个外显子3 kb内的5'调控区域。根据其在纯合ciD胚胎中不存在这一情况,鉴定出了假定的ciD转录本。其在发育过程中的空间表达模式不同寻常,与大多数其他体节基因不同,它在整个细胞胚盘和原肠胚形成过程中呈现均匀表达,直到胚带伸长快速期结束时才分解为周期性模式,此时它沿胚胎前后轴以15条宽的节段重复条纹形式存在。ciD表达条纹相对于其他体节极性基因条纹的定位表明,ciD在每个体节的前三分之二部分表达。这种定位与ciD突变体中观察到的模式缺陷不相关。序列分析表明,ciD转录本编码的蛋白质包含一个由五个串联氨基酸重复组成的结构域,这些重复与非洲爪蟾转录因子TFIIIA的锌指重复序列具有序列相似性,并且与人类锌指蛋白GLI具有最高程度的同一性,已发现该蛋白在几种人类胶质母细胞瘤中发生扩增。