During pancreatic development, proliferating pancreatic progenitors activate the proendocrine transcription factor neurogenin 3 (NEUROG3), exit the cell cycle, and differentiate into islet cells. The mechanisms that direct robust NEUROG3 expression within a subset of progenitor cells control the size of the endocrine population. Here we demonstrate that NEUROG3 is phosphorylated within the nucleus on serine 183, which catalyzes its hyperphosphorylation and proteosomal degradation. During progression through the progenitor cell cycle, NEUROG3 phosphorylation is driven by the actions of cyclin-dependent kinases 2 and 4/6 at G1/S cell-cycle checkpoint. Using models of mouse and human pancreas development, we show that lengthening of the G1 phase of the pancreatic progenitor cell cycle is essential for proper induction of NEUROG3 and initiation of endocrine cell differentiation. In sum, these studies demonstrate that progenitor cell-cycle G1 lengthening, through its actions on stabilization of NEUROG3, is an essential variable in normal endocrine cell genesis.
Pubmed ID: 28441528 RIS Download
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Software tool to enable biologists without training in computer vision or programming to quantitatively measure phenotypes from thousands of images automatically. It counts cells and also measures the size, shape, intensity and texture of every cell (and every labeled subcellular compartment) in every image. It was designed for high throughput screening but can perform automated image analysis for images from time-lapse movies and low-throughput experiments. CellProfiler has an increasing number of algorithms to identify and measure properties of neuronal cell types.
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View all literature mentionsThis polyclonal targets Phospho-Histone H3 (Ser10)
View all literature mentionsThis polyclonal targets Human Neurogenin-3 Affinity Purified Ab
View all literature mentionsThis polyclonal targets RCJMB04_4h19
View all literature mentionsThis unknown targets p27 Kip1
View all literature mentionsThis unknown targets Human Chromogranin A
View all literature mentionsThis monoclonal targets pancreatic duodenal homeobox protein 1 (Pdx1)
View all literature mentionsThis monoclonal targets neurogenin 3
View all literature mentionsThis monoclonal targets Glucagon
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets Insulin
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsMus musculus with name Crl:CD1(ICR) from IMSR.
View all literature mentionsMus musculus with name C57BL/6-Tg(tetO-Cdkn1b)1Scpr/J from IMSR.
View all literature mentionsMus musculus with name B6.129S4-Krastm4Tyj/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Pdx1-cre)89.1Dam/Mmucd from MMRRC.
View all literature mentionsMus musculus with name Crl:CD1(ICR) from IMSR.
View all literature mentionsThis polyclonal targets Mouse Carboxypeptidase A1 Affinity Purified Ab
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