Delay in development and behavioural abnormalities in the absence of p53 in zebrafish

Seham Elabd1,2, Nuzhat Amna Jabeen1, Vanessa Gerber1

  • 1Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Eggenstein-Leopoldshafen, Germany.

Plos One
|July 20, 2019
PubMed

Insights

The tumor suppressor p53 (p53) is crucial for early zebrafish development and larval behavior. While p53-deficient embryos show initial delays, compensatory mechanisms allow partial recovery, though hatching and activity remain impaired.

Area of Science:

  • Developmental Biology
  • Genetics
  • Neuroscience

Background:

  • The tumor suppressor protein p53 is known for its role in cancer suppression.
  • Emerging evidence highlights p53's involvement in stem cell regulation, differentiation, and animal development.
  • The precise function of p53 in early embryonic development requires further elucidation.

Purpose of the Study:

  • To investigate the role of p53 in the early embryonic development and behavior of zebrafish (Danio rerio).
  • To characterize developmental and behavioral phenotypes in p53-deficient zebrafish using CRISPR/Cas9 technology.

Main Methods:

  • Generation of p53 knockout zebrafish using CRISPR/Cas9 gene editing.
  • Observation and analysis of embryonic and larval development, including pigmentation, eye size, and body length.
  • Assessment of behavioral parameters such as activity levels, travel distance, and response to stimuli (vibration, touch).
  • Quantitative analysis of p63 and p73 expression levels in p53-deficient embryos.

Main Results:

  • p53-deficient zebrafish embryos exhibited delayed early development.
  • A partial recovery in development was observed after 1 day post-fertilization (dpf), with similar pigmentation and eye size compared to wild-type siblings.
  • Hatching time remained significantly delayed in p53 knockout zebrafish.
  • p53 deficiency led to reduced larval activity, decreased travel distance, and increased latency to move.
  • Overexpression of p63 and p73 was noted in p53-deficient embryos, suggesting a compensatory mechanism.

Conclusions:

  • p53 plays a significant role in regulating the pace of early embryonic development in zebrafish.
  • Compensatory mechanisms involving p53 family members (p63, p73) can partially rescue developmental delays.
  • Despite compensatory effects, p53 is essential for normal hatching times and coordinated locomotion activities in zebrafish larvae.

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