PUBLICATION
Depletion of Bhmt Elevates sonic hedgehog Transcript Level and Increases β-Cell Number in Zebrafish
- Authors
- Yang, S.L., Aw, S.S., Chang, C., Korzh, S., Korzh, V., and Peng, J.
- ID
- ZDB-PUB-111013-4
- Date
- 2011
- Source
- Endocrinology 152(12): 4706-17 (Journal)
- Registered Authors
- Korzh, Vladimir, Peng, Jinrong, Yang, Shulan
- Keywords
- none
- MeSH Terms
-
- Animals
- Betaine-Homocysteine S-Methyltransferase/deficiency
- Betaine-Homocysteine S-Methyltransferase/physiology*
- Cell Count
- Embryo, Nonmammalian/physiology
- Gene Expression Regulation, Developmental
- Hedgehog Proteins/genetics*
- Insulin-Secreting Cells/cytology*
- Organogenesis/physiology
- RNA, Messenger/analysis
- Up-Regulation
- Zebrafish
- Zebrafish Proteins/genetics*
- PubMed
- 21952238 Full text @ Endocrinology
Citation
Yang, S.L., Aw, S.S., Chang, C., Korzh, S., Korzh, V., and Peng, J. (2011) Depletion of Bhmt Elevates sonic hedgehog Transcript Level and Increases β-Cell Number in Zebrafish. Endocrinology. 152(12):4706-17.
Abstract
Betaine homocysteine S-methyltransferase (BHMT, EC 2.1.1.5) is a key enzyme in the methionine cycle and is highly expressed in the liver. Despite its important biochemical function, it is not known whether BHMT plays a role during organ development. In this report, we showed that early in development of zebrafish before endoderm organogenesis, bhmt is first expressed in the yolk syncytial layer and then after liver formation becomes a liver-enriched gene. By using the anti-bhmt morpholinos that deplete the Bhmt, we found that in morphant embryos, several endoderm-derived organs, including liver, exocrine pancreas, and intestine are hypoplastic. Strikingly, the number of β-cells in the pancreatic islet was increased rather than reduced in the morphant. Additional studies showed that Bhmt depletion elevates the sonic hedgehog (shh) transcript level in the morphant, whereas Bhmt-depletion in the Shh-deficient mutant syu failed to rescue the isletless phenotype. These molecular and genetic data strongly suggest that Shh functions downstream of Bhmt to promote β-cell development. Therefore, although there are still many intriguing questions to be answered, our finding may identify a novel function for Bhmt involving modulation of Shh signaling to control β-cell development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping