PUBLICATION

Zebrafish mnx1 controls cell fate choice in the developing endocrine pancreas

Authors
Dalgin, G., Ward, A.B., Hao le, T., Beattie, C.E., Nechiporuk, A., and Prince, V.E.
ID
ZDB-PUB-111026-6
Date
2011
Source
Development (Cambridge, England)   138(21): 4597-4608 (Journal)
Registered Authors
Beattie, Christine, Dalgin, Gokhan, Nechiporuk, Alex, Prince, Victoria E., Ward, Andrea B.
Keywords
zebrafish, pancreas, mnx1, hb9, retinoic acid
MeSH Terms
  • Islets of Langerhans/cytology
  • Islets of Langerhans/embryology*
  • Islets of Langerhans/growth & development
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Organogenesis/physiology*
  • Animals
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Tretinoin/metabolism
  • Genes, Reporter
  • Gene Expression Regulation, Developmental
  • Cell Lineage
  • Animals, Genetically Modified
  • Stem Cells/cytology
  • Stem Cells/physiology
  • Humans
  • Cell Differentiation/physiology*
  • Signal Transduction
  • Zebrafish/anatomy & histology
  • Zebrafish/embryology*
  • Zebrafish/growth & development
  • Endoderm/cytology
  • Endoderm/physiology
(all 24)
PubMed
21989909 Full text @ Development
Abstract

The vertebrate endocrine pancreas has the crucial function of maintaining blood sugar homeostasis. This role is dependent upon the development and maintenance of pancreatic islets comprising appropriate ratios of hormone-producing cells. In all vertebrate models studied, an initial precursor population of Pdx1-expressing endoderm cells gives rise to separate endocrine and exocrine cell lineages. Within the endocrine progenitor pool a variety of transcription factors influence cell fate decisions, such that hormone-producing differentiated cell types ultimately arise, including the insulin-producing beta cells and the antagonistically acting glucagon-producing alpha cells. In previous work, we established that the development of all pancreatic lineages requires retinoic acid (RA) signaling. We have used the zebrafish to uncover genes that function downstream of RA signaling, and here we identify mnx1 (hb9) as an RA-regulated endoderm transcription factor-encoding gene. By combining manipulation of gene function, cell transplantation approaches and transgenic reporter analysis we establish that Mnx1 functions downstream of RA within the endoderm to control cell fate decisions in the endocrine pancreas progenitor lineage. We confirm that Mnx1-deficient zebrafish lack beta cells, and, importantly, we make the novel observation that they concomitantly gain alpha cells. In Mnx1-deficient embryos, precursor cells that are normally destined to differentiate as beta cells instead take on an alpha cell fate. Our findings suggest that Mnx1 functions to promote beta and suppress alpha cell fates.

Genes / Markers
Figures
Figure Gallery (18 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ha01TgTransgenic Insertion
    nl1TgTransgenic Insertion
      os26TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        mnx1MO1-mnx1MRPHLNO
        mnx1MO2-mnx1MRPHLNO
        sox32MO1-sox32MRPHLNO
        1 - 3 of 3
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        Fish
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab1-gcgmonoclonal
          IgG1Mouse
          Ab1-inspolyclonalGuinea pig
          ab1-sstpolyclonal
            IgGRabbit
            Ab2-islmonoclonalIgG2bMouse
            Ab4-h3polyclonal
              IgGRabbit
              Ab8-casp3polyclonal
                Rabbit
                Ab-A4.1025monoclonal
                  IgG2aMouse
                  1 - 7 of 7
                  Show
                  Orthology
                  No data available
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  EGFPEFGEGFP
                  1 - 1 of 1
                  Show
                  Mapping
                  No data available