• Bechard ME, Bankaitis ED, Ustione A, Piston DW, Magnuson MA, Wright CVE. FUCCI tracking shows cell-cycle-dependent Neurog3 variation in pancreatic progenitors. Genesis (New York, N.Y. : 2000). 2017 Aug 2. PMID: 28772022 [PubMed].

Abstract 

During pancreas organogenesis, Neurog3(HI) endocrine-committing cells are generated from a population of Sox9(+) mitotic progenitors with only a low level of Neurog3 transcriptional activity (Neurog3(TA.LO) ). Low-level Neurog3 protein, in Neurog3(TA.LO) cells, is required to maintain their mitotic endocrine-lineage-primed status. Herein, we describe a Neurog3-driven FUCCI cell-cycle reporter (Neurog3(P2A.FUCCI) ) derived from a Neurog3 BAC transgenic reporter that functions as a loxed cassette acceptor (LCA). In cycling Sox9(+) Neurog3(TA.LO) progenitors, the majority of cells in S-G2 -M phases have undetectable levels of Neurog3 with increased expression of endocrine progenitor markers, while those in G1 have low Neurog3 levels with increased expression of endocrine differentiation markers. These findings support a model in which variations in Neurog3 protein levels are coordinated with cell-cycle phase progression in Neurog3(TA.LO) progenitors with entrance into G1 triggering a concerted effort, beyond increasing Neurog3 levels, to maintain an endocrine-lineage-primed state by initiating expression of the downstream endocrine differentiation program prior to endocrine-commitment. This article is protected by copyright. All rights reserved.