PUBLICATION
Nom1 Mediates Pancreas Development by Regulating Ribosome Biogenesis in Zebrafish
- Authors
- Qin, W., Chen, Z., Zhang, Y., Yan, R., Yan, G., Li, S., Zhong, H., Lin, S.
- ID
- ZDB-PUB-140627-4
- Date
- 2014
- Source
- PLoS One 9: e100796 (Journal)
- Registered Authors
- Lin, Shuo, Zhong, Hanbing
- Keywords
- none
- MeSH Terms
-
- Gene Expression Regulation, Developmental
- Ribosomes/metabolism*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- RNA Splicing
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism*
- Nuclear Proteins/genetics
- Nuclear Proteins/metabolism*
- Organogenesis*
- Animals
- Pancreas/embryology*
- Humans
- RNA, Messenger/genetics
- Cell Nucleolus/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Mutation
- PubMed
- 24967912 Full text @ PLoS One
Citation
Qin, W., Chen, Z., Zhang, Y., Yan, R., Yan, G., Li, S., Zhong, H., Lin, S. (2014) Nom1 Mediates Pancreas Development by Regulating Ribosome Biogenesis in Zebrafish. PLoS One. 9:e100796.
Abstract
Ribosome biogenesis is an important biological process for proper cellular function and development. Defects leading to improper ribosome biogenesis can cause diseases such as Diamond-Blackfan anemia and Shwachman-Bodian-Diamond syndrome. Nucleolar proteins are a large family of proteins and are involved in many cellular processes, including the regulation of ribosome biogenesis. Through a forward genetic screen and positional cloning, we identified and characterized a zebrafish line carrying mutation in nucleolar protein with MIF4G domain 1 (nom1), which encodes a conserved nulceolar protein with a role in pre-rRNA processing. Zebrafish nom1 mutants exhibit major defects in endoderm development, especially in exocrine pancreas. Further studies revealed that impaired proliferation of ptf1a-expressing pancreatic progenitor cells mainly contributed to the phenotype. RNA-seq and molecular analysis showed that ribosome biogenesis and pre-mRNA splicing were both affected in the mutant embryos. Several defects of ribosome assembly have been shown to have a p53-dependent mechanism. In the nom1 mutant, loss of p53 did not rescue the pancreatic defect, suggesting a p53-independent role. Further studies indicate that protein phosphatase 1 alpha, an interacting protein to Nom1, could partially rescue the pancreatic defect in nom1 morphants if a human nucleolar localization signal sequence was artificially added. This suggests that targeting Pp1α into the nucleolus by Nom1 is important for pancreatic proliferation. Altogether, our studies revealed a new mechanism involving Nom1 in controlling vertebrate exocrine pancreas formation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping