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Published on: October 27, 2023
Manipulation of Interrenal Cell Function in Developing Zebrafish Using Genetically Targeted Ablation and an
Jose Arturo Gutierrez-Triana1, Ulrich Herget1, Luis A Castillo-Ramirez1
1Developmental Genetics of the Nervous System (J.A.G.-T., U.H., L.A.C.-R., M.L., C.-M.Y., R.J.D.M., S.R.), Max Planck Institute for Medical Research, D-69120 Heidelberg, Germany; and The Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology (U.H., L.A.C.-R.), University of Heidelberg, D-69120 Germany.
Researchers developed a new transgenic method in zebrafish to control cortisol levels. This technique allows for precise manipulation of the hypothalamic-pituitary-adrenal/interrenal axis, aiding studies on hormone regulation and stress responses.
Area of Science:
- Endocrinology
- Neuroscience
- Zebrafish models
Background:
- The hypothalamic-pituitary-adrenal/interrenal axis regulates stress responses via glucocorticoids.
- Understanding cortisol's role in zebrafish is crucial due to conserved mechanisms.
- Existing pharmacological methods have limitations for specific manipulation.
Purpose of the Study:
- To develop a novel transgenic approach for precise manipulation of cortisol levels in zebrafish.
- To enable the study of both low (hypocortisolemia) and high (hypercortisolemia) cortisol conditions.
Main Methods:
- Utilized the steroidogenic acute regulatory protein promoter to target gene expression in interrenal cells.
- Generated a transgenic line for conditional ablation of interrenal cells using bacterial nitroreductase.
- Developed a system for blue light-dependent induction of cortisol using optogenetics (Beggiatoa photoactivated adenylyl cyclase).
Main Results:
- Successfully created a transgenic line enabling targeted ablation of interrenal cells.
- Demonstrated significant reduction in basal and stress-induced cortisol levels post-ablation.
- Established an optogenetic method to increase cortisol production in a light-dependent manner.
Conclusions:
- The developed transgenic approach provides a robust tool for manipulating interrenal cell activity in zebrafish.
- This method allows for specific control over endogenous cortisol concentrations, facilitating studies on its physiological and pathological effects.
- Enables detailed investigation into the consequences of altered cortisol levels on zebrafish physiology and behavior.
