Loss of ctnnd2b affects neuronal differentiation and behavior in zebrafish

Raquel Vaz1, Steven Edwards2, Alfredo Dueñas-Rey1

  • 1Department of Molecular Medicine and Surgery and Centre of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

PubMed

Insights

Heterozygous loss of delta-catenin (CTNND2) disrupts zebrafish brain development and increases activity. This suggests CTNND2’s role in neuronal differentiation and behavior, potentially linking to neurodevelopmental disorders.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Delta-catenin (CTNND2) is an adhesive junction protein linked to neurodevelopmental disorders.
  • The human CTNND2 gene is located in a region deleted in Cri-du-chat syndrome.
  • Heterozygous CTNND2 loss is associated with autism, schizophrenia, and intellectual disability.

Purpose of the Study:

  • To investigate the impact of heterozygous loss of delta-catenin specifically in zebrafish (ctnnd2b) on embryonic development and adult behavior.
  • To identify specific neuronal abnormalities in the developing zebrafish brain.
  • To analyze behavioral changes in zebrafish larvae and adults with ctnnd2b loss.

Main Methods:

  • Zebrafish model organism utilized for studying gene function.
  • Observation of embryonic development and neuronal subtype organization (e.g., isl1, GABA).
  • Time-lapse imaging to analyze neuron specification and distribution.
  • Behavioral analysis of larval and adult zebrafish swimming patterns.

Main Results:

  • Observed disorganization of neuronal subtypes in the developing zebrafish forebrain.
  • Identified ectopic isl1-expressing cells and reduced GABA-positive neurons in the optic recess region.
  • Time-lapse analysis revealed increased specification of Isl1:GFP neurons.
  • Heterozygous ctnnd2b zebrafish exhibited increased swimming activity in both larval and adult stages.

Conclusions:

  • Zebrafish ctnnd2b plays a crucial role in the differentiation of specific neuronal subtypes within the vertebrate brain.
  • Disruption of ctnnd2b impacts neuronal development, leading to observable behavioral changes.
  • These findings contribute to understanding the genetic basis of neurodevelopmental disorders associated with CTNND2.

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