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Abnormal nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-deficient zebrafish


De Jong-Curtain, TA and Parslow, AC and Trotter, AJ and Hall, NE and Verkade, H and Tabone, T and Christie, EL and Crowhurst, MO and Layton, JE and Shepherd, IT and Nixon, SJ and Parton, RG and Zon, LI and Stainier, DYR and Lieschke, GJ and Heath, JK, Abnormal nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-deficient zebrafish, Gastroenterology, 136, (3) pp. 902-911. ISSN 0016-5085 (2009) [Refereed Article]

Copyright Statement

2009 by the AGA Institute

DOI: doi:10.1053/j.gastro.2008.11.012


Background & Aims: Zebrafish mutants generated by ethylnitrosourea-mutagenesis provide a powerful tool for dissecting the genetic regulation of developmental processes, including organogenesis. One zebrafish mutant, "flotte lotte" (flo), displays striking defects in intestinal, liver, pancreas, and eye formation at 78 hours postfertilization (hpf). In this study, we sought to identify the underlying mutated gene in flo and link the genetic lesion to its phenotype.

Methods: Positional cloning was employed to map the flo mutation. Subcellular characterization of flo embryos was achieved using histology, immunocytochemistry, bromodeoxyuridine incorporation analysis, and confocal and electron microscopy.

Results: The molecular lesion in flo is a nonsense mutation in the elys (embryonic large molecule derived from yolk sac) gene, which encodes a severely truncated protein lacking the Elys C-terminal AT-hook DNA binding domain. Recently, the human ELYS protein has been shown to play a critical, and hitherto unsuspected, role in nuclear pore assembly. Although elys messenger RNA (mRNA) is expressed broadly during early zebrafish development, widespread early defects in flo are circumvented by the persistence of maternally expressed elys mRNA until 24 hpf. From 72 hpf, elys mRNA expression is restricted to proliferating tissues, including the intestinal epithelium, pancreas, liver, and eye. Cells in these tissues display disrupted nuclear pore formation; ultimately, intestinal epithelial cells undergo apoptosis.

Conclusions: Our results demonstrate that Elys regulates digestive organ formation.

Item Details

Item Type:Refereed Article
Keywords:zebrafish, elys, nuclear pore, apoptosis, intestinal epithelium, intestinal abnormalities
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell development, proliferation and death
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Trotter, AJ (Dr Andrew Trotter)
ID Code:118739
Year Published:2009
Web of Science® Times Cited:36
Deposited By:Directorate
Deposited On:2017-07-19
Last Modified:2017-08-04

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