Abnormal Nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-Deficient zebrafish

De Jong-Curtain, Tanya A., Parslow, Adam C., Trotter, Andrew J., Hall , Nathan E., Verkade, Heather, Tabone, Tania, Christie, Elizabeth L., Crowhurst, Meredith O., Layton, Judith E., Shepherd, Iain T., Nixon, Susan J., Parton, Robert G., Zon. Leonard I., Stainier, Didier Y.R., Lieschke, Graham J. and Heath, Joan K. (2009) Abnormal Nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-Deficient zebrafish. Gastroenterology, 136 3: 902-911.e7.


Author De Jong-Curtain, Tanya A.
Parslow, Adam C.
Trotter, Andrew J.
Hall , Nathan E.
Verkade, Heather
Tabone, Tania
Christie, Elizabeth L.
Crowhurst, Meredith O.
Layton, Judith E.
Shepherd, Iain T.
Nixon, Susan J.
Parton, Robert G.
Zon. Leonard I.
Stainier, Didier Y.R.
Lieschke, Graham J.
Heath, Joan K.
Title Abnormal Nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-Deficient zebrafish
Formatted title Abnormal nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-Deficient zebrafish
Journal name Gastroenterology  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2009-03
Sub-type Article
Year available 2009
DOI 10.1053/j.gastro.2008.11.012
Volume number 136
Issue number 3
ISSN 0016-5085: 1528-0012
Start page 902
End page 911.e7
Total pages 17
Place of publication New York, NY, United States
Publisher Elsevier
Collection year 2009
Language eng
Subject C1
060110 Receptors and Membrane Biology
970106 Expanding Knowledge in the Biological Sciences
Formatted abstract 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article
Collections: 2009 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Created: Mon, 06 Apr 2009, 10:14:00 EST by Cody Mudgway on behalf of Institute for Molecular Bioscience