PUBLICATION

Plexina4 and cell survival in the developing zebrafish hindbrain

Authors
Nurcombe, Z.W., Hehr, C.L., McFarlane, S.
ID
ZDB-PUB-230608-31
Date
2023
Source
Developmental Dynamics : an official publication of the American Association of Anatomists   252(11): 1323-1337 (Journal)
Registered Authors
Hehr, Carrie, McFarlane, Sarah
Keywords
CRISPR mutant, Clusterin, apoptosis, embryo, floor plate, motor neuron
MeSH Terms
  • Animals
  • Axons/metabolism
  • Cell Survival/genetics
  • Clusterin*/metabolism
  • Gene Expression Regulation, Developmental
  • Rhombencephalon/metabolism
  • Zebrafish*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
(all 9)
PubMed
37283310 Full text @ Dev. Dyn.
Abstract
Background Growth factors are important in the developing and mature nervous system to support the survival of neurons. Developmental signaling molecules are known for their roles in controlling neurogenesis and neural circuit formation. Whether or not these molecules also have roles in cell survival in the developing nervous system is poorly understood. Plexins are a family of transmembrane receptors that bind Semaphorin ligands and are known to function in the guidance of developing axons and blood vessels.
Results In embryonic zebrafish, plexina4 is expressed widely in the brain, becoming largely restricted to the hindbrain as neurogenesis and differentiation proceed. Apoptosis is increased in the embryonic hindbrain of a plexina4ca307/ca307 CRISPR mutant. Based on the literature, we tested the secreted heat shock protein, Clusterin, as a candidate ligand to mediate cell survival through Plexina4. clusterin is expressed by the floor plate of the embryonic zebrafish hindbrain, in proximity to plexina4-expressing hindbrain cells. Morpholino-mediated knockdown of Clusterin increases cell apoptosis in the hindbrain, with additional cell death observed in epistasis experiments where Clusterin is knocked down in a plexina4 mutant background.
Conclusions Our data suggest that Plexina4 promotes cell survival in the developing zebrafish hindbrain, likely through a pathway independent of Clusterin.
Genes / Markers
Marker Marker Type Name
bhlhe40GENEbasic helix-loop-helix family, member e40
cluGENEclusterin
fgf8aGENEfibroblast growth factor 8a
foxa2GENEforkhead box A2
foxg1aGENEforkhead box G1a
pax6aGENEpaired box 6a
plxna4GENEplexin A4
sema3faGENEsema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3Fa
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Figures
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ca307
    		Indel
    zc7TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      bhlhe40MO1-bhlhe40MRPHLNO
      cluCRISPR1-cluCRISPR
      cluMO1-cluMRPHLNO
      plxna4CRISPR3-plxna4CRISPR
      1 - 4 of 4
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      Fish
      No data available
      Antibodies
      Orthology
      Engineered Foreign Genes
      Marker Marker Type Name
      GFPEFGGFP
      1 - 1 of 1
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      Mapping
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      Citation
      Nurcombe, Z.W., Hehr, C.L., McFarlane, S. (2023) Plexina4 and cell survival in the developing zebrafish hindbrain. Developmental Dynamics : an official publication of the American Association of Anatomists. 252(11):1323-1337.