Investigating the role of dachshund b in the development of the pancreatic islet in zebrafish

Lingling Yang, Sarah E. Webb, Nana Jin, Heung Man Lee, Ting Fung Chan, Gang XU, Juliana C.N. Chan, Andrew L. Miller, Ronald C.W. Ma*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 messenger ribonucleic acid, and determined the effect on the development of the pancreatic islet. We also carried out quantitative polymerase chain reaction and ribonucleic acid sequencing 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 messenger ribonucleic acid. Knockdown of dachb was associated with a significant downregulation 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, ribonucleic sequencing analysis showed an upregulation of genes enriched in the forkhead box O and mitogen-activated protein kinase signaling pathways in the dachb-MO group, when compared with the control groups. Conclusions: Together, our results suggest the possible role of dachb in islet development in zebrafish.

Original languageEnglish
Pages (from-to)710-727
Number of pages18
JournalJournal of Diabetes Investigation
Volume12
Issue number5
DOIs
Publication statusPublished - May 2021

Scopus Subject Areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

User-Defined Keywords

  • dachshund b
  • Pancreatic islet development
  • Zebrafish

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