A scalable and tunable platform for functional interrogation of peptide hormones in fish
Pituitary hormones play a central role in shaping vertebrate life history events, including growth, reproduction, metabolism, and aging. The regulation of these traits often requires precise control of hormone levels across diverse timescales. However, fine tuning circulating hormones in-vivo has tr...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/85960 |
| _version_ | 1797652522075160576 |
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| author | Eitan Moses Roman Franek Itamar Harel |
| author_facet | Eitan Moses Roman Franek Itamar Harel |
| author_sort | Eitan Moses |
| collection | DOAJ |
| description | Pituitary hormones play a central role in shaping vertebrate life history events, including growth, reproduction, metabolism, and aging. The regulation of these traits often requires precise control of hormone levels across diverse timescales. However, fine tuning circulating hormones in-vivo has traditionally been experimentally challenging. Here, using the naturally short-lived turquoise killifish (N. furzeri), we describe a high-throughput platform that combines loss- and gain-of-function of peptide hormones. Mutation of three primary pituitary hormones, growth hormone (gh1), follicle stimulating hormone (fshb), and thyroid stimulating hormone (tshb), alters somatic growth and reproduction. Thus, suggesting that while the killifish undergoes extremely rapid growth and maturity, it still relies on vertebrate-conserved genetic networks. As the next stage, we developed a gain-of-function vector system in which a hormone is tagged using a self-cleavable fluorescent reporter, and ectopically expressed in-vivo through intramuscular electroporation. Following a single electroporation, phenotypes, such as reproduction, are stably rescued for several months. Notably, we demonstrate the versatility of this approach by using multiplexing, dose-dependent, and doxycycline-inducible systems to achieve tunable and reversible expression. In summary, this method is relatively high-throughput, and facilitates large-scale interrogation of life-history strategies in fish. Ultimately, this approach could be adapted for modifying aquaculture species and exploring pro-longevity interventions. |
| first_indexed | 2024-03-11T16:31:06Z |
| format | Article |
| id | doaj.art-494ad11d6b2346048c151a88925c73d4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-11T16:31:06Z |
| publishDate | 2023-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-494ad11d6b2346048c151a88925c73d42023-10-24T06:30:45ZengeLife Sciences Publications LtdeLife2050-084X2023-10-011210.7554/eLife.85960A scalable and tunable platform for functional interrogation of peptide hormones in fishEitan Moses0https://orcid.org/0000-0003-0090-335XRoman Franek1https://orcid.org/0000-0002-3464-1872Itamar Harel2https://orcid.org/0000-0001-9749-8279Department of Genetics, the Silberman Institute, The Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Genetics, the Silberman Institute, The Hebrew University of Jerusalem, Jerusalem, Israel; University of South Bohemia in Ceske Budejovice, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Vodnany, Czech RepublicDepartment of Genetics, the Silberman Institute, The Hebrew University of Jerusalem, Jerusalem, IsraelPituitary hormones play a central role in shaping vertebrate life history events, including growth, reproduction, metabolism, and aging. The regulation of these traits often requires precise control of hormone levels across diverse timescales. However, fine tuning circulating hormones in-vivo has traditionally been experimentally challenging. Here, using the naturally short-lived turquoise killifish (N. furzeri), we describe a high-throughput platform that combines loss- and gain-of-function of peptide hormones. Mutation of three primary pituitary hormones, growth hormone (gh1), follicle stimulating hormone (fshb), and thyroid stimulating hormone (tshb), alters somatic growth and reproduction. Thus, suggesting that while the killifish undergoes extremely rapid growth and maturity, it still relies on vertebrate-conserved genetic networks. As the next stage, we developed a gain-of-function vector system in which a hormone is tagged using a self-cleavable fluorescent reporter, and ectopically expressed in-vivo through intramuscular electroporation. Following a single electroporation, phenotypes, such as reproduction, are stably rescued for several months. Notably, we demonstrate the versatility of this approach by using multiplexing, dose-dependent, and doxycycline-inducible systems to achieve tunable and reversible expression. In summary, this method is relatively high-throughput, and facilitates large-scale interrogation of life-history strategies in fish. Ultimately, this approach could be adapted for modifying aquaculture species and exploring pro-longevity interventions.https://elifesciences.org/articles/85960nothobranchius furzeripeptide hormonessomatic growthreproductionagingaquaculture |
| spellingShingle | Eitan Moses Roman Franek Itamar Harel A scalable and tunable platform for functional interrogation of peptide hormones in fish eLife nothobranchius furzeri peptide hormones somatic growth reproduction aging aquaculture |
| title | A scalable and tunable platform for functional interrogation of peptide hormones in fish |
| title_full | A scalable and tunable platform for functional interrogation of peptide hormones in fish |
| title_fullStr | A scalable and tunable platform for functional interrogation of peptide hormones in fish |
| title_full_unstemmed | A scalable and tunable platform for functional interrogation of peptide hormones in fish |
| title_short | A scalable and tunable platform for functional interrogation of peptide hormones in fish |
| title_sort | scalable and tunable platform for functional interrogation of peptide hormones in fish |
| topic | nothobranchius furzeri peptide hormones somatic growth reproduction aging aquaculture |
| url | https://elifesciences.org/articles/85960 |
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