PUBLICATION
Investigating the role of dachshund b in the development of the pancreatic islet in zebrafish
- Authors
- Yang, L., Webb, S.E., Jin, N., Lee, H.M., Chan, T.F., Xu, G., Chan, J.C.N., Miller, A.L., Ma, R.C.W.
- ID
- ZDB-PUB-210116-9
- Date
- 2021
- Source
- Journal of diabetes investigation 12(5): 710-727 (Journal)
- Registered Authors
- Miller, Andrew L., Webb, Sarah E.
- Keywords
- dachshund b, diabetes, islet development, zebrafish, β-cells
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics*
- Embryonic Development/genetics
- Gene Expression/genetics
- Islets of Langerhans/embryology*
- Morpholinos
- Pancreas/embryology
- Pancreas/growth & development
- Zebrafish/genetics*
- Zebrafish Proteins/physiology*
- PubMed
- 33449448 Full text @ J Diabetes Investig
Citation
Yang, L., Webb, S.E., Jin, N., Lee, H.M., Chan, T.F., Xu, G., Chan, J.C.N., Miller, A.L., Ma, R.C.W. (2021) Investigating the role of dachshund b in the development of the pancreatic islet in zebrafish. Journal of diabetes investigation. 12(5):710-727.
Abstract
Aims/introduction β-cell dysfunction is a hallmark of type 2 diabetes. In a previous pilot study, we identified an association between genetic variants within the human DACH1 gene and young-onset type 2 diabetes. Here, we characterized the function of dachb, the only dach homologue to be expressed in the pancreas, in developing zebrafish embryos.
Materials and methods We injected one-cell stage embryos with a dachb-morpholino (MO) or with the dachb-MO and dachb-mRNA and determined the effect on the development of the pancreatic islet. We also conducted qPCR and RNA-seq on the dachb-MO group to determine the effect of dachb knockdown on gene expression.
Results MO-mediated dachb knockdown resulted in impaired islet cell development, with a significant decrease in both the β-cell and islet cell numbers. This islet developmental defect was rescued when embryos were co-injected with dachb-MO and dachb-mRNA. Knockdown of dachb was associated with a significant down-regulation of the β-cell specific marker gene insa and the somatostatin cell marker sst2, as well as regulators of pancreas development, ptf1a, neuroD, pax6a and nkx6.1, and the cell cycle gene, insm1a. Furthermore, RNA-seq analysis indicated an up-regulation of genes enriched in the FoxO and MAPK signaling pathways in the dachb-MO group, when compared with the control groups.
Conclusion Together, our results suggest the possible role of dachb in islet development in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping