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
{"title":"Patched和Costal-2突变导致组织过度生长自主性的差异。","authors":"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","doi":"10.1080/19336934.2022.2062991","DOIUrl":null,"url":null,"abstract":"<p><p>Genetic screens are used in <i>Drosophila melanogaster</i> 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 <i>Drosophila</i>. Here, we have used an FLP/FRT mosaic system to screen for conditional regulators of cell growth and cell division in the <i>Drosophila</i> 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 <i>Ptc</i> mutation and here we add to the understanding of disrupting the Hh pathway with a novel allele of <i>Cos2</i>. Both of these Hh components are negative regulators of the pathway, yet they depict mutant differences in the type of overgrowth created. <i>Ptc</i> mutations lead to overgrowth consisting of almost entirely wild-type tissue (non-autonomous overgrowth), while the <i>Cos2</i> 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 <i>Drosophila</i> 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.</p>","PeriodicalId":12128,"journal":{"name":"Fly","volume":"16 1","pages":"176-189"},"PeriodicalIF":2.4000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045829/pdf/","citationCount":"0","resultStr":"{\"title\":\"<i>Patched</i> and <i>Costal-2</i> mutations lead to differences in tissue overgrowth autonomy.\",\"authors\":\"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\",\"doi\":\"10.1080/19336934.2022.2062991\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Genetic screens are used in <i>Drosophila melanogaster</i> 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 <i>Drosophila</i>. Here, we have used an FLP/FRT mosaic system to screen for conditional regulators of cell growth and cell division in the <i>Drosophila</i> 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 <i>Ptc</i> mutation and here we add to the understanding of disrupting the Hh pathway with a novel allele of <i>Cos2</i>. Both of these Hh components are negative regulators of the pathway, yet they depict mutant differences in the type of overgrowth created. <i>Ptc</i> mutations lead to overgrowth consisting of almost entirely wild-type tissue (non-autonomous overgrowth), while the <i>Cos2</i> 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 <i>Drosophila</i> 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.</p>\",\"PeriodicalId\":12128,\"journal\":{\"name\":\"Fly\",\"volume\":\"16 1\",\"pages\":\"176-189\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2022-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045829/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Fly\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/19336934.2022.2062991\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fly","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/19336934.2022.2062991","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Patched and Costal-2 mutations lead to differences in tissue overgrowth autonomy.
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.
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.