Maternal and Zygotic aldh1a2 Activity Is Required for Pancreas Development in Zebrafish
Open Access
- 11 December 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (12), e8261
- https://doi.org/10.1371/journal.pone.0008261
Abstract
We have isolated and characterized a novel zebrafish pancreas mutant. Mutant embryos lack expression of isl1 and sst in the endocrine pancreas, but retain isl1 expression in the CNS. Non-endocrine endodermal gene expression is less affected in the mutant, with varying degrees of residual expression observed for pdx1, carbA, hhex, prox1, sid4, transferrin and ifabp. In addition, mutant embryos display a swollen pericardium and lack fin buds. Genetic mapping revealed a mutation resulting in a glycine to arginine change in the catalytic domain of the aldh1a2 gene, which is required for the production of retinoic acid from vitamin A. Comparison of our mutant (aldh1a2um22) to neckless (aldh1a2i26), a previously identified aldh1a2 mutant, revealed similarities in residual endodermal gene expression. In contrast, treatment with DEAB (diethylaminobenzaldehyde), a competitive reversible inhibitor of Aldh enzymes, produces a more severe phenotype with complete loss of endodermal gene expression, indicating that a source of Aldh activity persists in both mutants. We find that mRNA from the aldh1a2um22 mutant allele is inactive, indicating that it represents a null allele. Instead, the residual Aldh activity is likely due to maternal aldh1a2, since we find that translation-blocking, but not splice-blocking, aldh1a2 morpholinos produce a phenotype similar to DEAB treatment. We conclude that Aldh1a2 is the primary Aldh acting during pancreas development and that maternal Aldh1a2 activity persists in aldh1a2um22 and aldh1a2i26 mutant embryos.Keywords
This publication has 67 references indexed in Scilit:
- Cyp26 enzymes function in endoderm to regulate pancreatic field sizeProceedings of the National Academy of Sciences of the United States of America, 2009
- Retinoic Acid Synthesis and Signaling during Early OrganogenesisCell, 2008
- The cdx Genes and Retinoic Acid Control the Positioning and Segmentation of the Zebrafish PronephrosPLoS Genetics, 2007
- RDH10 is essential for synthesis of embryonic retinoic acid and is required for limb, craniofacial, and organ developmentGenes & Development, 2007
- Vhnf1 acts downstream of Bmp, Fgf, and RA signals to regulate endocrine beta cell development in zebrafishDevelopmental Biology, 2007
- Dynamic and sequential patterning of the zebrafish posterior hindbrain by retinoic acidDevelopmental Biology, 2005
- Dorsal pancreas agenesis in retinoic acid-deficient Raldh2 mutant miceDevelopmental Biology, 2005
- A conserved role for retinoid signaling in vertebrate pancreas developmentWilhelm Roux' Archiv für Entwicklungsmechanik der Organismen, 2004
- Formation of the digestive system in zebrafish. ii. pancreas morphogenesis☆Developmental Biology, 2003
- Stages of embryonic development of the zebrafishDevelopmental Dynamics, 1995