J Comp Neurol 1996 Nov 18;3753:457-66. doi: 10.1002/(SICI)1096-9861(19961118)375:3<457::AID-CNE8>3.0.CO;2-1.

Spatial and temporal shifts in the regulation of neurogenesis in a peripheral ganglion.

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In the cardiac ganglion of the frog Xenopus laevis, the number of cholinergic neurons increases over several months. During this time, each neuron must insert itself into the control circuit of the functioning heart. Like all neurons, increases in cell number depend on the timing of both proliferation and differentiation of neuronal precursors. The characteristics of the cardiac ganglion provided an opportunity to test how proliferation and differentiation regulate the production of a specific population of neurons. The prolonged accumulation of cardiac neurons suggested that their site of origin shifted from the neural crest migratory pathway to the heart at later stages of development. 3H-thymidine labeling of neurons in organ culture confirmed that neuronal precursors in the heart divide over a period of at least 3 weeks of development. Quantitative analysis of individual cardiac neurons subjected to different labeling and sampling protocols provided an estimate of their cell cycle length. It also showed that the rate of neuron proliferation during normal development matched the rate of neuron accumulation. Labeling DNA and blocking its synthesis indicated that the time of cardiac neuron differentiation was variable, but the range did not change as the site of cardiac neurogenesis shifted. On the other hand, the regular proliferation of cardiac neuron precursors during the first few days of development slowed or stopped at later times. This change in regulation of neuronal precursor proliferation occurred during their change in location.

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