Genome-wide analysis identifies Homothorax and Extradenticle as regulators of insulin in Drosophila Insulin-Producing cells.
Drosophila Insulin-Producing Cells (IPCs) are the main production site of the Drosophila Insulin-like peptides or dilps which have key roles in regulating growth, development, reproduction, lifespan and metabolism. To better understand the signalling pathways and transcriptional networks that are ac...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-09-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1010380 |
| _version_ | 1817979555518873600 |
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| author | Mattias Winant Kurt Buhler Jason Clements Sofie De Groef Korneel Hens Veerle Vulsteke Patrick Callaerts |
| author_facet | Mattias Winant Kurt Buhler Jason Clements Sofie De Groef Korneel Hens Veerle Vulsteke Patrick Callaerts |
| author_sort | Mattias Winant |
| collection | DOAJ |
| description | Drosophila Insulin-Producing Cells (IPCs) are the main production site of the Drosophila Insulin-like peptides or dilps which have key roles in regulating growth, development, reproduction, lifespan and metabolism. To better understand the signalling pathways and transcriptional networks that are active in the IPCs we queried publicly available transcriptome data of over 180 highly inbred fly lines for dilp expression and used dilp expression as the input for a Genome-wide association study (GWAS). This resulted in the identification of variants in 125 genes that were associated with variation in dilp expression. The function of 57 of these genes in the IPCs was tested using an RNAi-based approach. We found that IPC-specific depletion of most genes resulted in differences in expression of one or more of the dilps. We then elaborated further on one of the candidate genes with the strongest effect on dilp expression, Homothorax, a transcription factor known for its role in eye development. We found that Homothorax and its binding partner Extradenticle are involved in regulating dilp2, -3 and -5 expression and that genetic depletion of both TFs shows phenotypes associated with reduced insulin signalling. Furthermore, we provide evidence that other transcription factors involved in eye development are also functional in the IPCs. In conclusion, we showed that this expression level-based GWAS approach identified genetic regulators implicated in IPC function and dilp expression. |
| first_indexed | 2024-04-13T22:43:16Z |
| format | Article |
| id | doaj.art-eb8ac901c4b44f1dbb330637b196446d |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-13T22:43:16Z |
| publishDate | 2022-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-eb8ac901c4b44f1dbb330637b196446d2022-12-22T02:26:31ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-09-01189e101038010.1371/journal.pgen.1010380Genome-wide analysis identifies Homothorax and Extradenticle as regulators of insulin in Drosophila Insulin-Producing cells.Mattias WinantKurt BuhlerJason ClementsSofie De GroefKorneel HensVeerle VulstekePatrick CallaertsDrosophila Insulin-Producing Cells (IPCs) are the main production site of the Drosophila Insulin-like peptides or dilps which have key roles in regulating growth, development, reproduction, lifespan and metabolism. To better understand the signalling pathways and transcriptional networks that are active in the IPCs we queried publicly available transcriptome data of over 180 highly inbred fly lines for dilp expression and used dilp expression as the input for a Genome-wide association study (GWAS). This resulted in the identification of variants in 125 genes that were associated with variation in dilp expression. The function of 57 of these genes in the IPCs was tested using an RNAi-based approach. We found that IPC-specific depletion of most genes resulted in differences in expression of one or more of the dilps. We then elaborated further on one of the candidate genes with the strongest effect on dilp expression, Homothorax, a transcription factor known for its role in eye development. We found that Homothorax and its binding partner Extradenticle are involved in regulating dilp2, -3 and -5 expression and that genetic depletion of both TFs shows phenotypes associated with reduced insulin signalling. Furthermore, we provide evidence that other transcription factors involved in eye development are also functional in the IPCs. In conclusion, we showed that this expression level-based GWAS approach identified genetic regulators implicated in IPC function and dilp expression.https://doi.org/10.1371/journal.pgen.1010380 |
| spellingShingle | Mattias Winant Kurt Buhler Jason Clements Sofie De Groef Korneel Hens Veerle Vulsteke Patrick Callaerts Genome-wide analysis identifies Homothorax and Extradenticle as regulators of insulin in Drosophila Insulin-Producing cells. PLoS Genetics |
| title | Genome-wide analysis identifies Homothorax and Extradenticle as regulators of insulin in Drosophila Insulin-Producing cells. |
| title_full | Genome-wide analysis identifies Homothorax and Extradenticle as regulators of insulin in Drosophila Insulin-Producing cells. |
| title_fullStr | Genome-wide analysis identifies Homothorax and Extradenticle as regulators of insulin in Drosophila Insulin-Producing cells. |
| title_full_unstemmed | Genome-wide analysis identifies Homothorax and Extradenticle as regulators of insulin in Drosophila Insulin-Producing cells. |
| title_short | Genome-wide analysis identifies Homothorax and Extradenticle as regulators of insulin in Drosophila Insulin-Producing cells. |
| title_sort | genome wide analysis identifies homothorax and extradenticle as regulators of insulin in drosophila insulin producing cells |
| url | https://doi.org/10.1371/journal.pgen.1010380 |
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