PUBLICATION

sept7b is required for the differentiation of pancreatic endocrine progenitors

Authors
Dash, S.N., Hakonen, E., Ustinov, J., Otonkoski, T., Andersson, O., Lehtonen, S.
ID
ZDB-PUB-160427-3
Date
2016
Source
Scientific Reports   6: 24992 (Journal)
Registered Authors
Keywords
Differentiation, Type 1 diabetes
MeSH Terms
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
  • Cell Differentiation
  • Islets of Langerhans/cytology*
  • Islets of Langerhans/metabolism
  • Septins/genetics*
  • Septins/metabolism*
  • Animals
  • Gene Knockout Techniques
  • Homeodomain Proteins/metabolism
  • Animals, Genetically Modified
  • Insulin-Secreting Cells/cytology
  • Insulin-Secreting Cells/metabolism
  • Glucagon-Secreting Cells/cytology
  • Glucagon-Secreting Cells/metabolism
  • Gene Expression Regulation, Developmental
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
  • Nerve Tissue Proteins/metabolism
  • Hedgehog Proteins/metabolism
  • Receptor, Notch1/metabolism
(all 22)
PubMed
27114183 Full text @ Sci. Rep.
Abstract
Protection or restoration of pancreatic β-cell mass as a therapeutic treatment for type 1 diabetes requires understanding of the mechanisms that drive the specification and development of pancreatic endocrine cells. Septins are filamentous small GTPases that function in the regulation of cell division, cytoskeletal organization and membrane remodeling, and are involved in various tissue-specific developmental processes. However, their role in pancreatic endocrine cell differentiation remains unknown. Here we show by functional manipulation techniques in transgenic zebrafish lines that suppression of sept7b, the zebrafish ortholog of human SEPT7, profoundly increases the number of endocrine progenitors but limits their differentiation, leading to reduction in β- and α-cell mass. Furthermore, we discovered that shh (sonic hedgehog) expression in the endoderm, essential for the development of pancreatic progenitors of the dorsal pancreatic bud, is absent in larvae depleted of sept7b. We also discovered that sept7b is important for the differentiation of ventral pancreatic bud-derived cells: sept7b-depleted larvae exhibit downregulation of Notch receptors notch1a and notch1b and show precocious differentiation of NeuroD-positive endocrine cells in the intrapancreatic duct and gut epithelium. Collectively, this study provides a novel insight into the development of pancreatic endocrine progenitors, revealing an essential role for sept7b in endocrine progenitor differentiation.
Genes / Markers
Figures
Figure Gallery (12 images) / 2
Show all Figures
Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WTchemical treatment by environment: glucoseDay 5
WTchemical treatment by environment: glucoseDay 5
WTchemical treatment by environment: glucoseDay 5
WT + MO1-septin15controlDay 5
WT + MO1-septin15controlDay 5
WT + MO1-septin15controlDay 5
WT + MO1-septin15controlDay 5
WT + MO1-septin15controlDay 5
WT + MO1-septin15standard conditions5-9 somites
WT + MO1-septin15standard conditionsPrim-5
1 - 10 of 36
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ia1TgTransgenic Insertion
    jh1TgTransgenic Insertion
      nl1TgTransgenic Insertion
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        septin15MO1-septin15MRPHLNO
        1 - 1 of 1
        Show
        Fish
        Fish
        ia1Tg
        ia1Tg + MO1-septin15
        jh1Tg
        jh1Tg + MO1-septin15
        nl1Tg
        nl1Tg + MO1-septin15
        WT
        WT + MO1-septin15
        1 - 8 of 8
        Show
        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        GFPEFGGFP
        1 - 2 of 2
        Show
        Mapping
        No data available
        Your Input Welcome
        We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
        Citation
        Dash, S.N., Hakonen, E., Ustinov, J., Otonkoski, T., Andersson, O., Lehtonen, S. (2016) sept7b is required for the differentiation of pancreatic endocrine progenitors. Scientific Reports. 6:24992.