PUBLICATION
Interference with the Cannabinoid Receptor CB1R Results in Miswiring of GnRH3 and AgRP1 Axons in Zebrafish Embryos
- Authors
- Zuccarini, G., D'Atri, I., Cottone, E., Mackie, K., Shainer, I., Gothilf, Y., Provero, P., Bovolin, P., Merlo, G.R.
- ID
- ZDB-PUB-191231-1
- Date
- 2019
- Source
- International Journal of Molecular Sciences 21(1): (Journal)
- Registered Authors
- Gothilf, Yoav, Shainer, Inbal
- Keywords
- AgRP, GnRH, axon guidance, cannabinoid receptor, neuroendocrine, stathmin, zebrafish
- MeSH Terms
-
- Agouti-Related Protein/metabolism*
- Animals
- Axons/metabolism*
- Benzoxazines/pharmacology
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Embryonic Development/drug effects
- Gonadotropin-Releasing Hormone/metabolism*
- Morpholines/pharmacology
- Morpholinos/metabolism
- Naphthalenes/pharmacology
- Neurons/drug effects
- Neurons/metabolism
- Pyrrolidonecarboxylic Acid/analogs & derivatives*
- Pyrrolidonecarboxylic Acid/metabolism
- Receptor, Cannabinoid, CB1/antagonists & inhibitors
- Receptor, Cannabinoid, CB1/genetics
- Receptor, Cannabinoid, CB1/metabolism*
- Zebrafish/growth & development
- Zebrafish/metabolism*
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 31881740 Full text @ Int. J. Mol. Sci.
Citation
Zuccarini, G., D'Atri, I., Cottone, E., Mackie, K., Shainer, I., Gothilf, Y., Provero, P., Bovolin, P., Merlo, G.R. (2019) Interference with the Cannabinoid Receptor CB1R Results in Miswiring of GnRH3 and AgRP1 Axons in Zebrafish Embryos. International Journal of Molecular Sciences. 21(1):.
Abstract
The G protein-coupled cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), and their endocannabinoid (eCBs) ligands, have been implicated in several aspects of brain wiring during development. Here we aim to assess whether interfering with CB1R affects development, neuritogenesis and pathfinding of GnRH and AgRP neurons, forebrain neurons that control respectively reproduction and appetite. We pharmacologically and genetically interfered with CB1R in zebrafish strains with fluorescently labeled GnRH3 and the AgRP1 neurons. By applying CB1R antagonists we observed a reduced number of GnRH3 neurons, fiber misrouting and altered fasciculation. Similar phenotypes were observed by CB1R knockdown. Interfering with CB1R also resulted in a reduced number, misrouting and poor fasciculation of the AgRP1 neuron's axonal projections. Using a bioinformatic approach followed by qPCR validation, we have attempted to link CB1R functions with known guidance and fasciculation proteins. The search identified stathmin-2, a protein controlling microtubule dynamics, previously demonstrated to be coexpressed with CB1R and now shown to be downregulated upon interference with CB1R in zebrafish. Together, these results raise the likely possibility that embryonic exposure to low doses of CB1R-interfering compounds could impact on the development of the neuroendocrine systems controlling sexual maturation, reproduction and food intake.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping