Loss of function of def selectively up-regulates Δ113p53 expression to arrest expansion growth of digestive organs in zebrafish

Jun Chen, Hua Ruan, Sok Meng Ng, Chuan Gao, Hui Meng Soo, Wei Wu, Zhenhai Zhang, Zilong Wen, David Lane, Jinrong Peng

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    130 Citations (Scopus)

    Abstract

    Transcription factor p53 forms a network with associated factors to regulate the cell cycle and apoptosis in response to environmental stresses. However, there is currently no direct genetic evidence to show if or how the p53 pathway functions during organogenesis. Here we present evidence to show that the zebrafish def (digestive-organ expansion factor) gene encodes a novel pan-endoderm-specific factor. A loss-of-function mutation in def confers hypoplastic digestive organs and selectively up-regulates the expression of ?113p53, counterpart to a newly identified isoform of p53 produced by an alternative internal promoter in intron 4 of the p53 gene in human. The increased ?113p53 expression is limited to within the mutant digestive organs, and this increase selectively induces the expression of p53-responsive genes to trigger the arrest of the cell cycle but not apoptosis, resulting in compromised organ growth in the mutant. Our data demonstrate that, while induction of expression of p53 and/or its isoforms is crucial to suppress abnormal cell growth, ?113p53 is tightly regulated by an organ/tissue-specific factor Def, especially during organogenesis, to prevent adverse inhibition of organ/tissue growth.
    Original languageEnglish
    Pages (from-to)2900-2911
    Number of pages12
    JournalGenes & Development
    Volume19
    Issue number23
    DOIs
    Publication statusPublished - Dec 2005

    Keywords

    • Def (digestive-organ expansion factor)
    • Endoderm organogenesis
    • p53
    • Zebrafish

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    Chen, J., Ruan, H., Ng, S. M., Gao, C., Soo, H. M., Wu, W., Zhang, Z., Wen, Z., Lane, D., & Peng, J. (2005). Loss of function of def selectively up-regulates Δ113p53 expression to arrest expansion growth of digestive organs in zebrafish. Genes & Development, 19(23), 2900-2911. https://doi.org/10.1101/gad.1366405