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Developmental Dynamics
Article . 2012 . Peer-reviewed
License: Wiley Online Library User Agreement
Data sources: Crossref
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Mapping differentiation kinetics in the mouse retina reveals an extensive period of cell cycle protein expression in post‐mitotic newborn neurons

Authors: Marek, Pacal; Rod, Bremner;

Mapping differentiation kinetics in the mouse retina reveals an extensive period of cell cycle protein expression in post‐mitotic newborn neurons

Abstract

AbstractBackground: Knowledge of gene expression kinetics around neuronal cell birth is required to dissect mechanisms underlying progenitor fate. Here, we timed cell cycle and neuronal protein silencing/induction during cell birth in the developing murine retina. Results: The pan‐cell cycle markers Pcna and Mcm6 were present in the post‐mitotic ganglion cell layer. Although confined to the neuroblastic layer (NBL), 6–7% of Ki67+ cells lacked six progenitor/cell cycle markers, and expressed neuronal markers. To define protein extinction/induction timing, we defined G2/M length throughout retinogenesis, which was typically 1–2 h, but <10% cells took double this time. BrdU‐chase analyses revealed that at E12.5, Tubb3 (Tuj1) appeared at M‐phase, followed by Calb2 and Dcx at ∼2 h, Elavl2/3/4 at ∼4 h, and Map2 at ∼6 h after cell birth, and these times extended with embryonic age. Strikingly, Ki67 was not extinguished until up to a day after cell cycle exit, coinciding with exit from the NBL and induction of late markers such as Map1b/Uchl1/Rbfox3. Conclusions: A minor population of progenitors transits slowly through G2/M and, most importantly, some cell cycle proteins are retained for an unexpectedly long period in post‐mitotic neurons. The high‐resolution map of cell birth kinetics reported here provides a framework to better define mechanisms that regulate neurogenesis. Developmental Dynamics 241:1525–1544, 2012. © 2012 Wiley Periodicals, Inc.

Keywords

Neurons, Doublecortin Protein, Microscopy, Confocal, Time Factors, Gene Expression Regulation, Developmental, Cell Cycle Proteins, Cell Differentiation, Minichromosome Maintenance Complex Component 6, Retina, G2 Phase Cell Cycle Checkpoints, Mice, Ki-67 Antigen, Animals, Newborn, Bromodeoxyuridine, Proliferating Cell Nuclear Antigen, Image Processing, Computer-Assisted, Animals

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    26
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
26
Top 10%
Average
Top 10%
bronze