PUBLICATION

Differential levels of Neurod establish zebrafish endocrine pancreas cell fates

Authors
Dalgin, G., Prince, V.E.
ID
ZDB-PUB-150325-11
Date
2015
Source
Developmental Biology   402(1): 81-97 (Journal)
Registered Authors
Dalgin, Gokhan, Prince, Victoria E.
Keywords
CRISPR, Glucagon, Insulin, Neurod, Notch, Pancreas, Phlorizin, Zebrafish
MeSH Terms
  • Mutagenesis
  • Glucose/chemistry
  • Gene Expression Regulation, Developmental*
  • Cell Lineage
  • Insulin-Secreting Cells/cytology*
  • RNA, Messenger/metabolism
  • Endocrine Cells/cytology
  • Glucagon-Secreting Cells/cytology*
  • Oligonucleotides, Antisense/chemistry
  • Glucagon/metabolism
  • Zebrafish/embryology*
  • Basic Helix-Loop-Helix Transcription Factors/physiology*
  • Benzazepines/chemistry
  • Insulin/metabolism
  • Phlorhizin/chemistry
  • Green Fluorescent Proteins/chemistry
  • Animals
  • Nerve Tissue Proteins/physiology*
  • Islets of Langerhans/embryology*
  • Cell Differentiation
(all 20)
PubMed
25797153 Full text @ Dev. Biol.
Abstract
During development a network of transcription factors functions to differentiate foregut cells into pancreatic endocrine cells. Differentiation of appropriate numbers of each hormone-expressing endocrine cell type is essential for the normal development of the pancreas and ultimately for effective maintenance of blood glucose levels. A fuller understanding of the details of endocrine cell differentiation may contribute to development of cell replacement therapies to treat diabetes. In this study, by using morpholino and gRNA/Cas9 mediated knockdown we establish that differential levels of the basic-helix loop helix (bHLH) transcription factor Neurod are required for the differentiation of distinct endocrine cell types in developing zebrafish. While Neurod plays a role in the differentiation of all endocrine cells, we find that differentiation of glucagon-expressing alpha cells is disrupted by a minor reduction in Neurod levels, whereas differentiation of insulin-expressing beta cells is less sensitive to Neurod depletion. The endocrine cells that arise during embryonic stages to produce the primary islet, and those that arise subsequently during larval stages from the intra-pancreatic duct (IPD) to ultimately contribute to the secondary islets, show similar dependence on differential Neurod levels. Intriguingly, Neurod-deficiency triggers premature formation of endocrine precursors from the IPD during early larval stages. However, the Neurod-deficient endocrine precursors fail to differentiate appropriately, and the larvae are unable to maintain normal glucose levels. In summary, differential levels of Neurod are required to generate endocrine pancreas subtypes from precursors during both embryonic and larval stages, and Neurod function is in turn critical to endocrine function.
Genes / Markers
Figures
Figure Gallery (20 images) / 2
Show all Figures
Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ha01TgTransgenic Insertion
    jh1TgTransgenic Insertion
      nl1TgTransgenic Insertion
        os26TgTransgenic Insertion
          1 - 4 of 4
          Show
          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          mnx1MO1-mnx1MRPHLNO
          mnx1MO2-mnx1MRPHLNO
          neurod1CRISPR1-neurod1CRISPR
          neurod1MO1-neurod1MRPHLNO
          neurod1MO2-neurod1MRPHLNO
          sox32MO1-sox32MRPHLNO
          1 - 6 of 6
          Show
          Fish
          Fish
          ha01Tg
          jh1Tg
          nl1Tg
          os26Tg
          1 - 4 of 4
          Show
          Antibodies
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          1 - 1 of 1
          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
          Dalgin, G., Prince, V.E. (2015) Differential levels of Neurod establish zebrafish endocrine pancreas cell fates. Developmental Biology. 402(1):81-97.