|ZFIN ID: ZDB-PUB-140627-4|
Nom1 Mediates Pancreas Development by Regulating Ribosome Biogenesis in Zebrafish
Qin, W., Chen, Z., Zhang, Y., Yan, R., Yan, G., Li, S., Zhong, H., Lin, S.
|Source:||PLoS One 9: e100796 (Journal)|
|Registered Authors:||Lin, Shuo, Zhong, Hanbing|
|PubMed:||24967912 Full text @ PLoS One|
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.
ABSTRACTRibosome 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.