RRC ID 39998
著者 Dalgin G, Prince VE.
タイトル Differential levels of Neurod establish zebrafish endocrine pancreas cell fates.
ジャーナル 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.
巻・号 402(1)
ページ 81-97
公開日 2015-6-1
DOI 10.1016/j.ydbio.2015.03.007
PII S0012-1606(15)00120-7
PMID 25797153
PMC PMC4433608
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / physiology* Benzazepines / chemistry Cell Differentiation Cell Lineage Endocrine Cells / cytology Gene Expression Regulation, Developmental* Glucagon / metabolism Glucagon-Secreting Cells / cytology* Glucose / chemistry Green Fluorescent Proteins / chemistry Insulin / metabolism Insulin-Secreting Cells / cytology* Islets of Langerhans / embryology* Mutagenesis Nerve Tissue Proteins / physiology* Oligonucleotides, Antisense / chemistry Phlorhizin / chemistry RNA, Messenger / metabolism Zebrafish / embryology*
IF 2.896
引用数 17
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
ゼブラフィッシュ Tg(sox17:EGFP)/ha01