PUBLICATION

Celsr3 drives development and connectivity of the acoustic startle hindbrain circuit

Authors
Meserve, J.H., Navarro, M.F., Ortiz, E.A., Granato, M.
ID
ZDB-PUB-241022-9
Date
2024
Source
PLoS Genetics   20: e1011415e1011415 (Journal)
Registered Authors
Granato, Michael
Keywords
none
MeSH Terms
  • Zebrafish*/genetics
  • Cadherins*/genetics
  • Cadherins*/metabolism
  • Axon Guidance/physiology
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • Cell Polarity/genetics
  • Frizzled Receptors/genetics
  • Frizzled Receptors/metabolism
  • Axons/metabolism
  • Axons/physiology
  • Neurons*/metabolism
  • Neurons*/physiology
  • Rhombencephalon*/metabolism
  • Reflex, Startle*/physiology
  • Animals
  • Synapses/genetics
  • Synapses/metabolism
  • Synapses/physiology
(all 19)
PubMed
39432544 Full text @ PLoS Genet.
Abstract
In the developing brain, groups of neurons organize into functional circuits that direct diverse behaviors. One such behavior is the evolutionarily conserved acoustic startle response, which in zebrafish is mediated by a well-defined hindbrain circuit. While numerous molecular pathways that guide neurons to their synaptic partners have been identified, it is unclear if and to what extent distinct neuron populations in the startle circuit utilize shared molecular pathways to ensure coordinated development. Here, we show that the planar cell polarity (PCP)-associated atypical cadherins Celsr3 and Celsr2, as well as the Celsr binding partner Frizzled 3a/Fzd3a, are critical for axon guidance of two neuron types that form synapses with each other: the command-like neuron Mauthner cells that drive the acoustic startle escape response, and spiral fiber neurons which provide excitatory input to Mauthner cells. We find that Mauthner axon growth towards synaptic targets is vital for Mauthner survival. We also demonstrate that symmetric spiral fiber input to Mauthner cells is critical for escape direction, which is necessary to respond to directional threats. Moreover, we identify distinct roles for Celsr3 and Celsr2, as Celsr3 is required for startle circuit development while Celsr2 is dispensable, though Celsr2 can partially compensate for loss of Celsr3 in Mauthner cells. This contrasts with facial branchiomotor neuron migration in the hindbrain, which requires Celsr2 while we find that Celsr3 is dispensable. Combined, our data uncover critical and distinct roles for individual PCP components during assembly of the acoustic startle hindbrain circuit.
Genes / Markers
Figures
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
a150TgTransgenic Insertion
    fh339
      Point Mutation
      fh447TgTransgenic Insertion
        j1229aGtTransgenic Insertion
          rw0TgTransgenic Insertion
            rw689
              Point Mutation
              s1999tTgTransgenic Insertion
                sa19274
                  Point Mutation
                  um60TgTransgenic Insertion
                    vo80TgTransgenic Insertion
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                      Human Disease / Model
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                      Sequence Targeting Reagents
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                      Fish
                      No data available
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      EGFPEFGEGFP
                      GAL4EFGGAL4
                      GFPEFGGFP
                      KaedeEFGKaede
                      mCherryEFGmCherry
                      1 - 5 of 5
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                      Mapping
                      No data available