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Molecular Physiology & Biophysics

FUCCI tracking shows cell-cycle-dependent Neurog3 variation in pancreatic progenitors.

AUTHORS

Bechard ME , Bankaitis ED , Ustione A , Piston DW , Magnuson MA , Wright CVE , . Genesis (New York, N.Y. : 2000). 2017 9 ; 55(9).

ABSTRACT

During pancreas organogenesis, Neurog3endocrine-committing cells are generated from a population of Sox9mitotic progenitors with only a low level of Neurog3 transcriptional activity (Neurog3). Low-level Neurog3 protein, in Neurog3cells, is required to maintain their mitotic endocrine-lineage-primed status. Herein, we describe a Neurog3-driven FUCCI cell-cycle reporter (Neurog3) derived from a Neurog3 BAC transgenic reporter that functions as a loxed cassette acceptor (LCA). In cycling Sox9Neurog3progenitors, the majority of cells in S-G-M phases have undetectable levels of Neurog3 with increased expression of endocrine progenitor markers, while those in Ghave 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 Neurog3progenitors with entrance into Gtriggering 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.

During pancreas organogenesis, Neurog3endocrine-committing cells are generated from a population of Sox9mitotic progenitors with only a low level of Neurog3 transcriptional activity (Neurog3). Low-level Neurog3 protein, in Neurog3cells, is required to maintain their mitotic endocrine-lineage-primed status. Herein, we describe a Neurog3-driven FUCCI cell-cycle reporter (Neurog3) derived from a Neurog3 BAC transgenic reporter that functions as a loxed cassette acceptor (LCA). In cycling Sox9Neurog3progenitors, the majority of cells in S-G-M phases have undetectable levels of Neurog3 with increased expression of endocrine progenitor markers, while those in Ghave 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 Neurog3progenitors with entrance into Gtriggering 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.

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