PUBLICATION

Agouti-Related Protein 2 Is a New Player in the Teleost Stress Response System

Authors
Shainer, I., Michel, M., Marquart, G.D., Bhandiwad, A.A., Zmora, N., Ben-Moshe Livne, Z., Zohar, Y., Hazak, A., Mazon, Y., Förster, D., Hollander-Cohen, L., Cone, R.D., Burgess, H.A., Gothilf, Y.
ID
ZDB-PUB-190611-2
Date
2019
Source
Current biology : CB   29(12): 2009-2019.e7 (Journal)
Registered Authors
Burgess, Harold, Cone, Roger, Gothilf, Yoav, Marquart, Gregory, Michel, Max, Shainer, Inbal, Zohar, Yonathan
Keywords
circadian clock, cortisol, food consumption, gene knockout, hypothalamus, neuronal ablation, pineal gland, single-cell RNA sequencing, transgenesis, zebrafish
Datasets
GEO:GSE123778
MeSH Terms
  • Animals
  • Gene Knockout Techniques
  • Hypothalamus/metabolism
  • Pineal Gland/metabolism
  • Stress, Physiological/genetics*
  • Zebrafish/genetics
  • Zebrafish/physiology*
PubMed
31178320 Full text @ Curr. Biol.
Abstract
Agouti-related protein (AgRP) is a hypothalamic regulator of food consumption in mammals. However, AgRP has also been detected in circulation, but a possible endocrine role has not been examined. Zebrafish possess two agrp genes: hypothalamically expressed agrp1, considered functionally equivalent to the single mammalian agrp, and agrp2, which is expressed in pre-optic neurons and uncharacterized pineal gland cells and whose function is not well understood. By ablation of AgRP1-expressing neurons and knockout of the agrp1 gene, we show that AgRP1 stimulates food consumption in the zebrafish larvae. Single-cell sequencing of pineal agrp2-expressing cells revealed molecular resemblance to retinal-pigment epithelium cells, and anatomic analysis shows that these cells secrete peptides, possibly into the cerebrospinal fluid. Additionally, based on AgRP2 peptide localization and gene knockout analysis, we demonstrate that pre-optic AgRP2 is a neuroendocrine regulator of the stress axis that reduces cortisol secretion. We therefore suggest that the ancestral role of AgRP was functionally partitioned in zebrafish by the two AgRPs, with AgRP1 centrally regulating food consumption and AgRP2 acting as a neuroendocrine factor regulating the stress axis.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes