PUBLICATION

The Ribosome Biogenesis Factor Ltv1 Is Essential for Digestive Organ Development and Definitive Hematopoiesis in Zebrafish

Authors
Zhang, C., Huang, R., Ma, X., Chen, J., Han, X., Li, L., Luo, L., Ruan, H., Huang, H.
ID
ZDB-PUB-211026-10
Date
2021
Source
Frontiers in cell and developmental biology   9: 704730 (Journal)
Registered Authors
Huang, Honghui, Li, Li, Luo, Lingfei, Ruan, Hua
Keywords
Ltv1, P53, digestive organs, hematopoiesis, ribosome biogenesis
MeSH Terms
none
PubMed
34692673 Full text @ Front Cell Dev Biol
Abstract
Ribosome biogenesis is a fundamental activity in cells. Ribosomal dysfunction underlies a category of diseases called ribosomopathies in humans. The symptomatic characteristics of ribosomopathies often include abnormalities in craniofacial skeletons, digestive organs, and hematopoiesis. Consistently, disruptions of ribosome biogenesis in animals are deleterious to embryonic development with hypoplasia of digestive organs and/or impaired hematopoiesis. In this study, ltv1, a gene involved in the small ribosomal subunit assembly, was knocked out in zebrafish by clustered regularly interspaced short palindromic repeats (CRISPRs)/CRISPR associated protein 9 (Cas9) technology. The recessive lethal mutation resulted in disrupted ribosome biogenesis, and ltv1Δ14/Δ14 embryos displayed hypoplastic craniofacial cartilage, digestive organs, and hematopoiesis. In addition, we showed that the impaired cell proliferation, instead of apoptosis, led to the defects in exocrine pancreas and hematopoietic stem and progenitor cells (HSPCs) in ltv1Δ14/Δ14 embryos. It was reported that loss of function of genes associated with ribosome biogenesis often caused phenotypes in a P53-dependent manner. In ltv1Δ14/Δ14 embryos, both P53 protein level and the expression of p53 target genes, Δ113p53 and p21, were upregulated. However, knockdown of p53 failed to rescue the phenotypes in ltv1Δ14/Δ14 larvae. Taken together, our data demonstrate that LTV1 ribosome biogenesis factor (Ltv1) plays an essential role in digestive organs and hematopoiesis development in zebrafish in a P53-independent manner.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ioz1TgTransgenic Insertion
    jh1TgTransgenic Insertion
      swu54
        Small Deletion
        swu55
          Indel
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          ltv1CRISPR1-ltv1CRISPR
          tp53MO4-tp53MRPHLNO
          1 - 2 of 2
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          Fish
          Antibodies
          Name Type Antigen Genes Isotypes Host Organism
          Ab-2F11monoclonalIgG1Mouse
          1 - 1 of 1
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          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          GFPEFGGFP
          1 - 2 of 2
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          Mapping
          No data available