Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/38754
Title: RA Signaling in Zebrafish Liver Development
Authors: NILESH KUMAR MAHAJAN
Keywords: zebrafish, retinoic-acid, liver-development, Raldh4, aldh8a1, rar-rxr
Issue Date: 12-Jan-2011
Source: NILESH KUMAR MAHAJAN (2011-01-12). RA Signaling in Zebrafish Liver Development. ScholarBank@NUS Repository.
Abstract: Zebrafish is one of the favorite organisms to study vertebrate development and its embryonic development has attributes that makes it a preferred organism to study liver organogenesis. Retinoic acid (RA) is a ligand for nuclear hormone receptor family RAR and RXR and an important regulator of vertebrate development, but its role in hepatogenesis remains elusive. In this study, we investigated the role of RA signaling in liver development using zebrafish as a model. Liver development was found to be inhibited upon exogenous RA treatment and chemical inhibitor of RA synthesis promoted liver development. Knockdown of raldh4 (Retinaldehyde dehydrogenase 4), a key enzyme for RA synthesis expressed in the developing liver, lead to suppression of liver formation. Correspondingly, overexpression of raldh4 resulted in liver enlargement. This apparent contradiction obtained with chemical treatment vis-a-vis genetic approaches might be due to various feedback loops involved in RA signaling or high RA precursor isomer specificity of Raldh4 enzyme. In addition to this knock-down of raldh4 caused severe disruption of early development, correlating with the widespread high expression of this gene in early embryos previously unrealized. Whole mount in situ hybridization analyses discovered that multiple RA receptors are expressed in zebrafish liver. Our results suggest that RA functions through its multiple receptors to influence liver organogenesis in zebrafish.
URI: http://scholarbank.nus.edu.sg/handle/10635/38754
Appears in Collections:Master's Theses (Open)

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