Patched and Costal-2 mutations lead to differences in tissue overgrowth autonomy.

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Fly Pub Date : 2022-12-01 DOI:10.1080/19336934.2022.2062991
Shannon L Moore, Frank C Adamini, Erik S Coopes, Dustin Godoy, Shyra J Northington, Jordan M Stewart, Richard L Tillett, Kayla L Bieser, Jacob D Kagey
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引用次数: 0

Abstract

Genetic screens are used in Drosophila melanogaster to identify genes key in the regulation of organismal development and growth. These screens have defined signalling pathways necessary for tissue and organismal development, which are evolutionarily conserved across species, including Drosophila. Here, we have used an FLP/FRT mosaic system to screen for conditional regulators of cell growth and cell division in the Drosophila eye. The conditional nature of this screen utilizes a block in the apoptotic pathway to prohibit the mosaic mutant cells from dying via apoptosis. From this screen, we identified two different mutants that mapped to the Hedgehog signalling pathway. Previously, we described a novel Ptc mutation and here we add to the understanding of disrupting the Hh pathway with a novel allele of Cos2. Both of these Hh components are negative regulators of the pathway, yet they depict mutant differences in the type of overgrowth created. Ptc mutations lead to overgrowth consisting of almost entirely wild-type tissue (non-autonomous overgrowth), while the Cos2 mutation results in tissue that is overgrown in both the mutant and wild-type clones (both autonomous and non-autonomous). These differences in tissue overgrowth are consistent in the Drosophila eye and wing. The observed difference is correlated with different deregulation patterns of pMad, the downstream effector of DPP signalling. This finding provides insight into pathway-specific differences that help to better understand intricacies of developmental processes and human diseases that result from deregulated Hedgehog signalling, such as basal cell carcinoma.

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Patched和Costal-2突变导致组织过度生长自主性的差异。
在黑腹果蝇中使用基因筛选来确定调控生物体发育和生长的关键基因。这些筛选确定了组织和机体发育所必需的信号通路,这些信号通路在包括果蝇在内的不同物种中是进化保守的。在这里,我们利用 FLP/FRT 镶嵌系统筛选果蝇眼睛中细胞生长和细胞分裂的条件调节因子。这种筛选的条件性质是利用凋亡途径的阻断来禁止镶嵌突变细胞通过凋亡死亡。通过这一筛选,我们发现了两种不同的突变体,它们映射到刺猬信号通路。此前,我们描述了一种新型的 Ptc 突变,在此,我们通过一种新型的 Cos2 等位基因,进一步加深了对 Hh 通路破坏的理解。这两种 Hh 通路元件都是该通路的负调控因子,但它们在造成过度生长的类型上存在突变差异。Ptc 突变导致的过度生长几乎完全由野生型组织组成(非自主性过度生长),而 Cos2 突变则导致突变体和野生型克隆中的组织都过度生长(自主性和非自主性)。这些组织过度生长的差异在果蝇的眼睛和翅膀中是一致的。观察到的差异与 DPP 信号的下游效应物 pMad 的不同失调模式有关。这一发现深入揭示了特定途径的差异,有助于更好地理解发育过程的复杂性以及因刺猬信号失调而导致的人类疾病,如基底细胞癌。
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来源期刊
Fly
Fly 生物-生化与分子生物学
CiteScore
2.90
自引率
0.00%
发文量
17
审稿时长
>12 weeks
期刊介绍: Fly is the first international peer-reviewed journal to focus on Drosophila research. Fly covers a broad range of biological sub-disciplines, ranging from developmental biology and organogenesis to sensory neurobiology, circadian rhythm and learning and memory, to sex determination, evolutionary biology and speciation. We strive to become the “to go” resource for every researcher working with Drosophila by providing a forum where the specific interests of the Drosophila community can be discussed. With the advance of molecular technologies that enable researchers to manipulate genes and their functions in many other organisms, Fly is now also publishing papers that use other insect model systems used to investigate important biological questions. Fly offers a variety of papers, including Original Research Articles, Methods and Technical Advances, Brief Communications, Reviews and Meeting Reports. In addition, Fly also features two unconventional types of contributions, Counterpoints and Extra View articles. Counterpoints are opinion pieces that critically discuss controversial papers questioning current paradigms, whether justified or not. Extra View articles, which generally are solicited by Fly editors, provide authors of important forthcoming papers published elsewhere an opportunity to expand on their original findings and discuss the broader impact of their discovery. Extra View authors are strongly encouraged to complement their published observations with additional data not included in the original paper or acquired subsequently.
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