PUBLICATION

A Forward Genetic Screen in Zebrafish Identifies the G-Protein-Coupled Receptor CaSR as a Modulator of Sensorimotor Decision Making

Authors
Jain, R.A., Wolman, M.A., Marsden, K.C., Nelson, J.C., Shoenhard, H., Echeverry, F.A., Szi, C., Bell, H., Skinner, J., Cobbs, E.N., Sawada, K., Zamora, A.D., Pereda, A.E., Granato, M.
ID
ZDB-PUB-180424-2
Date
2018
Source
Current biology : CB   28(9): 1357-1369.e5 (Journal)
Registered Authors
Granato, Michael, Jain, Roshan, Marsden, Kurt, Wolman, Marc
Keywords
AP2S1, CaSR, behavior choice, calcium-sensing receptor, decision making, genetic screen, startle response, zebrafish
MeSH Terms
  • Acoustic Stimulation
  • Animals
  • Behavior, Animal
  • Calcium/metabolism
  • Decision Making*
  • Genetic Testing
  • Mutation*
  • Psychomotor Performance*
  • Zebrafish/embryology
  • Zebrafish/physiology*
(all 10)
PubMed
29681477 Full text @ Curr. Biol.
Abstract
Animals continuously integrate sensory information and select contextually appropriate responses. Here, we show that zebrafish larvae select a behavioral response to acoustic stimuli from a pre-existing choice repertoire in a context-dependent manner. We demonstrate that this sensorimotor choice is modulated by stimulus quality and history, as well as by neuromodulatory systems-all hallmarks of more complex decision making. Moreover, from a genetic screen coupled with whole-genome sequencing, we identified eight mutants with deficits in this sensorimotor choice, including mutants of the vertebrate-specific G-protein-coupled extracellular calcium-sensing receptor (CaSR), whose function in the nervous system is not well understood. We demonstrate that CaSR promotes sensorimotor decision making acutely through Gαi/o and Gαq/11 signaling, modulated by clathrin-mediated endocytosis. Combined, our results identify the first set of genes critical for behavioral choice modulation in a vertebrate and reveal an unexpected critical role for CaSR in sensorimotor decision making.
Genes / Markers
Figures
Figure Gallery (4 images)
Show all Figures
Expression
Phenotype
Fish Conditions Stage Phenotype Figure
TLchemical treatment by environment: forskolinDay 5
TLchemical treatment by environment: phorbol 13-acetate 12-myristateDay 5
TLchemical treatment by environment: rolipramDay 5
TLchemical treatment by environment: serotoninDay 5
WIKchemical treatment by environment: serotoninDay 5
WIKchemical treatment by environment: dopamine agonistDay 5
ap2s1p172/p172standard conditionsDay 5
ap2s1p172/p172; casrp190/p190standard conditionsDay 5
biasdp197/dp197controlDay 5
bltnp193/p193controlDay 5
1 - 10 of 19
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b1
    		Point Mutation
    b4
      		Insertion
      b5
        		Small Deletion
        nkhspGFF62ATgTransgenic Insertion
          nkhspgffdmc130AEtTransgenic Insertion
            p172
              		Point Mutation
              p190
                		Point Mutation
                p191
                  		Unknown
                  p192
                    		Unknown
                    p193
                      		Unknown
                      1 - 10 of 17
                      Show
                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      Fish
                      ap2s1p172/p172
                      ap2s1p172/p172; casrp190/p190
                      biasdp197/dp197
                      bltnp193/p193
                      casrp190/p190
                      casrp190/p190; nkhspgffdmc130AEt; p201Tg
                      fashp191/p191
                      indcp195/p195
                      lrspp196/p196
                      nkhspgffdmc130AEt; p201Tg
                      1 - 10 of 14
                      Show
                      Antibodies
                      Orthology
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CitrineEFGCitrine
                      GAL4FFEFGGAL4FF
                      1 - 2 of 2
                      Show
                      Mapping
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                      Citation
                      Jain, R.A., Wolman, M.A., Marsden, K.C., Nelson, J.C., Shoenhard, H., Echeverry, F.A., Szi, C., Bell, H., Skinner, J., Cobbs, E.N., Sawada, K., Zamora, A.D., Pereda, A.E., Granato, M. (2018) A Forward Genetic Screen in Zebrafish Identifies the G-Protein-Coupled Receptor CaSR as a Modulator of Sensorimotor Decision Making. Current biology : CB. 28(9):1357-1369.e5.