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

<jats:title>Abstract</jats:title><jats:p><jats:styled-content>Background:</jats:styled-content> 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. <jats:styled-content>Results:</jats:styled-content> 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<jats:sup>+</jats:sup> 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. <jats:styled-content>Conclusions:</jats:styled-content> 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.</jats:p>