Proliferation and in vivo cell cycle dynamics in the SNS vs the DRG

      We compared in vivo cell cycle dynamics of developing thoracic dorsal root ganglia (DRG) and sympathetic stellate ganglia (StG). We used Sox10-immunohistochemistry to mark neural crest cells (NCCs) and glial cells and Tuj1 to mark neuroblasts and neurons. In the DRG, from E9.5-E11.5, the proportion of cycling cells (the growth fraction, GF) for NCCs (Sox10+ cells) is 100%, the cell cycle length (Tc) is short (~10 h) and S-phase (Ts) accounts for ~65% of the Tc. This ratio of Ts/Tc is maintained up until E13.5 when Tc dramatically increases and Ts shortens. This corresponds to when the first Sox10+ cells withdraw from the cell cycle. The first DRG neurons, marked by expression of Tuj1, appear between E9.5 and E10.5 as they withdraw permanently from the cell cycle. In the StG at E9.5, division of Sox10+ NCCs is rapid (Tc = 10.6 h) with a relatively long Ts. At E10.5, Sox10+ cells lengthened their Tc to 38 h and the Ts decreased. The first StG neuroblasts (Tuj1+ cells) appear on E10.5 and immediately exit the cell cycle, only to re-enter the cell cycle one day later at E11.5, when >80% of cells in the StG were Tuj1+ neuroblasts. Tuj1+ neuroblasts continued to cycle, with the first neuroblasts withdrawing permanently from the cell cycle after E12.5. While the pattern of proliferation was quite different in the two ganglia, with StG neuroblasts re-entering the cell cycle and continuing to proliferate rapidly after differentiation while DRG neurons permanently withdraw from the cell cycle on differentiation, in both tissues major changes in patterns of proliferation were marked by dramatic changes in cell cycle dynamics. This is consistent with the idea that significant changes in cell cycle parameters can alter the time available for signals to effect changes in cell behaviour.
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