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

Seham Elabd, Nuzhat Amna Jabeen, Vanessa Gerber, Ravindra Peravali, Jean-Christoph Bourdon, Shilpa Kancherla, Daniela Vallone, Christine Blattner (Lead / Corresponding author)

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Abstract

p53 is well-known for its tumour-suppressive activity. However, in the past decade it became clear that p53 is also involved in other processes including stem cell proliferation, differentiation and animal development. To investigate the role of p53 in early embryonic development, we targeted p53 by CRISPR/Cas9 to make a p53 knock-out zebrafish (Danio rerio). Our data show developmental and behavioural effects in p53-deficient zebrafish embryos and larvae. Specifically, we found that early development of zebrafish was clearly delayed in the absence of p53. However, after 1 day (1 dpf), the p53-deficient embryos appeared to recover, as evidenced by a similar level of pigmentation at 26 hpf, similar size of the eye at 4 dpf and only a minor difference in body size at 4 dpf compared to p53 wild-type siblings. The recovery of development after 1 dpf in p53-deficient embryos could be due to a compensatory mechanism involving other p53 family members. p63 and p73 were found over-expressed with respect to wild-type siblings. However, despite this adaptation, the hatching time remained delayed in p53-/- zebrafish. In addition to differences in development, p53-null zebrafish embryos also showed differences in behaviour. We observed an overall reduced activity and a reduced travel distance under non-stressed conditions and after exposing the larvae to vibration. We also observed a longer latency until the larvae started to move after touching with a needle. Overall, these data indicate that p53 is involved in early development and locomotion activities.

Original languageEnglish
Article numbere0220069
Number of pages18
JournalPLoS ONE
Volume14
Issue number7
DOIs
Publication statusPublished - 19 Jul 2019

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Clustered Regularly Interspaced Short Palindromic Repeats
Cell proliferation
Zebrafish
Stem cells
Danio rerio
Needles
Tumors
Animals
Recovery
embryo (animal)
Embryonic Structures
Larva
early development
Siblings
larvae
animal development
Pigmentation
Body Size
Locomotion
Vibration

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Elabd, S., Jabeen, N. A., Gerber, V., Peravali, R., Bourdon, J-C., Kancherla, S., ... Blattner, C. (2019). Delay in development and behavioural abnormalities in the absence of p53 in zebrafish. PLoS ONE, 14(7), [e0220069]. https://doi.org/10.1371/journal.pone.0220069
Elabd, Seham ; Jabeen, Nuzhat Amna ; Gerber, Vanessa ; Peravali, Ravindra ; Bourdon, Jean-Christoph ; Kancherla, Shilpa ; Vallone, Daniela ; Blattner, Christine. / Delay in development and behavioural abnormalities in the absence of p53 in zebrafish. In: PLoS ONE. 2019 ; Vol. 14, No. 7.
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abstract = "p53 is well-known for its tumour-suppressive activity. However, in the past decade it became clear that p53 is also involved in other processes including stem cell proliferation, differentiation and animal development. To investigate the role of p53 in early embryonic development, we targeted p53 by CRISPR/Cas9 to make a p53 knock-out zebrafish (Danio rerio). Our data show developmental and behavioural effects in p53-deficient zebrafish embryos and larvae. Specifically, we found that early development of zebrafish was clearly delayed in the absence of p53. However, after 1 day (1 dpf), the p53-deficient embryos appeared to recover, as evidenced by a similar level of pigmentation at 26 hpf, similar size of the eye at 4 dpf and only a minor difference in body size at 4 dpf compared to p53 wild-type siblings. The recovery of development after 1 dpf in p53-deficient embryos could be due to a compensatory mechanism involving other p53 family members. p63 and p73 were found over-expressed with respect to wild-type siblings. However, despite this adaptation, the hatching time remained delayed in p53-/- zebrafish. In addition to differences in development, p53-null zebrafish embryos also showed differences in behaviour. We observed an overall reduced activity and a reduced travel distance under non-stressed conditions and after exposing the larvae to vibration. We also observed a longer latency until the larvae started to move after touching with a needle. Overall, these data indicate that p53 is involved in early development and locomotion activities.",
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Elabd, S, Jabeen, NA, Gerber, V, Peravali, R, Bourdon, J-C, Kancherla, S, Vallone, D & Blattner, C 2019, 'Delay in development and behavioural abnormalities in the absence of p53 in zebrafish', PLoS ONE, vol. 14, no. 7, e0220069. https://doi.org/10.1371/journal.pone.0220069

Delay in development and behavioural abnormalities in the absence of p53 in zebrafish. / Elabd, Seham; Jabeen, Nuzhat Amna; Gerber, Vanessa; Peravali, Ravindra; Bourdon, Jean-Christoph; Kancherla, Shilpa; Vallone, Daniela; Blattner, Christine (Lead / Corresponding author).

In: PLoS ONE, Vol. 14, No. 7, e0220069, 19.07.2019.

Research output: Contribution to journalArticle

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AU - Jabeen, Nuzhat Amna

AU - Gerber, Vanessa

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AU - Bourdon, Jean-Christoph

AU - Kancherla, Shilpa

AU - Vallone, Daniela

AU - Blattner, Christine

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