Sonic Hedgehog Signaling Switches the Mode of Division in the Developing Nervous System

• A switch in the mode of cell division controls motor neuron generation
• A mathematical model predicts the timing for the developmental switch
• Sonic hedgehog inhibition is required for the switch in the mode of division
• Cell-cycle parameters readjust in response to Sonic hedgehog instructing stemness

SummaryThe different modes of stem cell division are tightly regulated to balance growth and differentiation during organ development and homeostasis, and these regulatory processes are subverted in tumor formation. Here, we developed markers that provided the single-cell resolution necessary to quantify the three modes of division taking place in the developing nervous system in vivo: self-expanding, PP; self-replacing, PN; and self-consuming, NN. Using these markers and a mathematical model that predicts the dynamics of motor neuron progenitor division, we identify a role for the morphogen Sonic hedgehog in the maintenance of stem cell identity in the developing spinal cord. Moreover, our study provides insight into the process linking lineage commitment to neurogenesis with changes in cell-cycle parameters. As a result, we propose a challenging model in which the external Sonic hedgehog signal dictates stem cell identity, reflected in the consequent readjustment of cell-cycle parameters.

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