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
-
- Nerve Tissue Proteins/physiology*
- Green Fluorescent Proteins/chemistry
- Animals
- Phlorhizin/chemistry
- Zebrafish/embryology*
- Glucose/chemistry
- Oligonucleotides, Antisense/chemistry
- Cell Differentiation
- Benzazepines/chemistry
- Cell Lineage
- Glucagon/metabolism
- Insulin/metabolism
- RNA, Messenger/metabolism
- Glucagon-Secreting Cells/cytology*
- Islets of Langerhans/embryology*
- Insulin-Secreting Cells/cytology*
- Gene Expression Regulation, Developmental*
- Basic Helix-Loop-Helix Transcription Factors/physiology*
- Mutagenesis
- Endocrine Cells/cytology
- PubMed
- 25797153 Full text @ Dev. Biol.
Citation
Dalgin, G., Prince, V.E. (2015) Differential levels of Neurod establish zebrafish endocrine pancreas cell fates. Developmental Biology. 402(1):81-97.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping