Function and regulation of zebrafish nkx2.2a during development of pancreatic islet and ducts

Pauls, S., Zecchin, E., Tiso, N., Bortolussi, M., and Argenton, F.
Developmental Biology   304(2): 875-890 (Journal)
Registered Authors
Argenton, Francesco, Bortolussi, Marino, Pauls, Stefan, Tiso, Natascia, Zecchin, Elisabetta
Zebrafish, Pancreas, Duct, Exocrine, Islet, Ghrelin, nkx2.2, ptf1a
MeSH Terms
  • Animals
  • Base Sequence
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins/metabolism*
  • Islets of Langerhans/cytology
  • Islets of Langerhans/embryology
  • Islets of Langerhans/metabolism*
  • Molecular Sequence Data
  • Pancreatic Ducts/cytology
  • Pancreatic Ducts/embryology
  • Pancreatic Ducts/metabolism*
  • Promoter Regions, Genetic
  • Transcription Factors/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/metabolism
17335795 Full text @ Dev. Biol.
In the mouse Nkx2.2 is expressed in the entire pancreatic anlage. Nevertheless, absence of Nkx2.2 only perturbs the development of endocrine cell types, notably beta-cells which are completely absent. In order to test the possibility that Nkx2.2 might fulfil additional functions during pancreas development we analysed its zebrafish homologue nkx2.2a using gene targeting and GFP-transgenic fish lines. Our results suggest similar roles for nkx2.2a and Nkx2.2 during the development of the endocrine pancreas. Morpholino-based knock-down of nkx2.2a leads to a reduction of alpha- and beta-cell number and an increase of ghrelin-producing cells but, as in mice, does not affect delta-cells. Moreover, like in the mouse, two spatially distinct promoters regulate expression of nkx2.2a in precursors and differentiated islet cells. In addition we found that in zebrafish nkx2.2a is also expressed in the anterior pancreatic bud and, later, in the differentiated pancreatic ducts. A nkx2.2a-transgenic line in which pancreatic GFP expression is restricted to the pancreatic ducts revealed that single GFP-positive cells leave the anterior pancreatic bud and move towards the islet where they form intercellular connections between each other. Subsequently, these cells generate the branched network of the larval pancreatic ducts. Morpholinos that block nkx2.2a function also lead to the absence of the pancreatic ducts. We observed the same phenotype in ptf1a-morphants that are additionally characterized by a reduced number of nkx2.2a-positive duct precursors. Whereas important details of the molecular program leading to the differentiation of endocrine cell types are conserved between mammals and zebrafish, our results reveal a new function for nkx2.2a in the development of the pancreatic ducts.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes