Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster.

Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster.
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DOI:
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发表时间:
1995-03
期刊:
影响因子:
3.3
通讯作者:
J. Sekelsky;S. Newfeld;L. Raftery;E. Chartoff;W. Gelbart
J. Sekelsky;S. Newfeld;L. Raftery;E. Chartoff;W. Gelbart
中科院分区:
生物学2区
文献类型:
--
作者:
J. Sekelsky;S. Newfeld;L. Raftery;E. Chartoff;W. Gelbart

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黑腹果蝇(Drosophila melanogaster)的decapentaplegic(dpp)基因编码属于转化生长因子-β(TGF-β)超家族的生长因子,并且在整个发育过程中的多个细胞-细胞信号传导事件中起核心作用。通过基因筛选,我们正在寻求确定其他功能,上游,下游或与dpp协调,以介导其信号作用。我们在这里报告的遗传特性和克隆的母亲对dpp(疯狂),在两个这样的屏幕上确定的基因。Mad功能丧失突变与DPP等位基因相互作用,以增强胚胎背腹图案缺陷,以及成人附件缺陷,这表明Mad在介导DPP功能的某些方面的作用。为了支持这一点,纯合Mad突变动物在中肠形态发生、成虫盘发育和胚胎背腹图案方面表现出缺陷,这非常令人想起dpp突变表型。我们克隆了Mad区域,并通过种系转化拯救鉴定了Mad转录单位。我们对Mad cDNA进行了测序,并确定了三个改变编码信息的Mad点突变。预测的MAD多肽缺乏已知的蛋白质基序,但具有很强的序列相似性,从线虫线虫的基因组序列预测的三个多肽。因此,MAD是一个新的,高度保守的蛋白质家族的成员。
The decapentaplegic (dpp) gene of Drosophila melanogaster encodes a growth factor that belongs to the transforming growth factor-beta (TGF-beta) superfamily and that plays a central role in multiple cell-cell signaling events throughout development. Through genetic screens we are seeking to identify other functions that act upstream, downstream or in concert with dpp to mediate its signaling role. We report here the genetic characterization and cloning of Mothers against dpp (Mad), a gene identified in two such screens. Mad loss-of-function mutations interact with dpp alleles to enhance embryonic dorsal-ventral patterning defects, as well as adult appendage defects, suggesting a role for Mad in mediating some aspect of dpp function. In support of this, homozygous Mad mutant animals exhibit defects in midgut morphogenesis, imaginal disk development and embryonic dorsal-ventral patterning that are very reminiscent of dpp mutant phenotypes. We cloned the Mad region and identified the Mad transcription unit through germline transformation rescue. We sequenced a Mad cDNA and identified three Mad point mutations that alter the coding information. The predicted MAD polypeptide lacks known protein motifs, but has strong sequence similarity to three polypeptides predicted from genomic sequence from the nematode Caenorhabditis elegans. Hence, MAD is a member of a novel, highly conserved protein family.