A scalable and tunable platform for functional interrogation of peptide hormones in fish

Eitan Moses, Roman Franek, Itamar Harel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageAmerican English
Article numbere85960
JournaleLife
Volume12
DOIs
StatePublished - 24 Oct 2023

Bibliographical note

Publisher Copyright:
© Moses et al.

Fingerprint

Dive into the research topics of 'A scalable and tunable platform for functional interrogation of peptide hormones in fish'. Together they form a unique fingerprint.

Cite this