PUBLICATION

In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis.

Authors
Freudenblum, J., Iglesias, J.A., Hermann, M., Walsen, T., Wilfinger, A., Meyer, D., Kimmel, R.A.
ID
ZDB-PUB-180202-2
Date
2018
Source
Development (Cambridge, England)   145(3): (Journal)
Registered Authors
Kimmel, Robin, Meyer, Dirk, Walsen, Tanja, Wilfinger, Armin
Keywords
Filopodia, Islet, Morphogenesis, PI3K, Pancreas, Zebrafish
MeSH Terms
  • Pseudopodia/metabolism
  • Pseudopodia/ultrastructure
  • Organogenesis
  • Animals, Genetically Modified
  • Keratin-18/genetics
  • Keratin-18/metabolism
  • Single-Cell Analysis
  • Receptors, G-Protein-Coupled/antagonists & inhibitors
  • Receptors, G-Protein-Coupled/genetics
  • Receptors, G-Protein-Coupled/metabolism
  • Actin Cytoskeleton/metabolism
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Islets of Langerhans/cytology
  • Islets of Langerhans/growth & development*
  • Islets of Langerhans/metabolism*
  • Cell Aggregation
  • rac1 GTP-Binding Protein/antagonists & inhibitors
  • rac1 GTP-Binding Protein/metabolism
  • Phosphatidylinositol 3-Kinases/antagonists & inhibitors
  • Phosphatidylinositol 3-Kinases/metabolism*
  • Cell Movement
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism*
  • Animals
  • Signal Transduction
(all 28)
PubMed
29386244 Full text @ Development
Abstract
The three-dimensional architecture of the pancreatic islet is integral to beta cell function, but the process of islet formation remains poorly understood due to the difficulties of imaging internal organs with cellular resolution. Within transparent zebrafish larvae, the developing pancreas is relatively superficial and thus amenable to live imaging approaches. We performed in vivo time-lapse and longitudinal imaging studies to follow islet development, visualizing both naturally occurring islet cells and cells arising with an accelerated timecourse following an induction approach. These studies revealed previously unappreciated fine dynamic protrusions projecting between neighboring and distant endocrine cells. Using pharmacological compound and toxin interference approaches, and single-cell analysis of morphology and cell dynamics, we determined that endocrine cell motility is regulated by phosphoinositide 3-kinase (PI3K) and G-protein-coupled receptor (GPCR) signaling. Linking cell dynamics to islet formation, perturbation of protrusion formation disrupted endocrine cell coalescence, and correlated with decreased islet cell differentiation. These studies identified novel cell behaviors contributing to islet morphogenesis, and suggest a model in which dynamic exploratory filopodia establish cell-cell contacts that subsequently promote cell clustering.
Genes / Markers
Figures
Figure Gallery (23 images) / 3
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gz2TgTransgenic Insertion
    ia1TgTransgenic Insertion
      jh1TgTransgenic Insertion
        ml4TgTransgenic Insertion
          ml11TgTransgenic Insertion
            ml35TgTransgenic Insertion
              ml36TgTransgenic Insertion
                ml37TgTransgenic Insertion
                  ml38TgTransgenic Insertion
                    ml39TgTransgenic Insertion
                      1 - 10 of 15
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      No data available
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      BPTXEFGBPTX
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GFPEFGGFP
                      mAGFPEFGmAGFP
                      mCherryEFGmCherry
                      mKOFP2EFGmKOFP2
                      NTREFGNTR
                      TomatoEFGTomato
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                      Citation
                      Freudenblum, J., Iglesias, J.A., Hermann, M., Walsen, T., Wilfinger, A., Meyer, D., Kimmel, R.A. (2018) In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis.. Development (Cambridge, England). 145(3).