Regeneration of several organs involves adaptive reprogramming of progenitors, but the intrinsic capacity of the developing brain to replenish lost cells remains largely unknown. Here we found that the developing cerebellum has unappreciated progenitor plasticity, since it undergoes near full growth and functional recovery following acute depletion of granule cells, the most plentiful neuron population in the brain. We demonstrate that following postnatal ablation of granule cell progenitors, Nestin-expressing progenitors, specified during mid-embryogenesis to produce astroglia and interneurons, switch their fate and generate granule neurons in mice. Moreover, Hedgehog signaling in two Nestin-expressing progenitor populations is crucial not only for the compensatory replenishment of granule neurons but also for scaling interneuron and astrocyte numbers. Thus, we provide insights into the mechanisms underlying robustness of circuit formation in the cerebellum and speculate that adaptive reprogramming of progenitors in other brain regions plays a greater role than appreciated in developmental regeneration.

中文翻译：

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Nestin +祖细胞的适应性重编程，可损伤小脑颗粒细胞。

几个器官的再生涉及祖细胞的适应性重编程，但是发育中的大脑补充丢失细胞的内在能力仍然未知。在这里，我们发现发育中的小脑没有明显的祖细胞可塑性，因为它在急性耗尽颗粒细胞（大脑中最丰富的神经元种群）后经历了近乎完全的生长和功能恢复。我们证明，在产后消融颗粒细胞祖细胞后，表达巢蛋白的祖细胞在胚胎发生中期指定以产生星形胶质细胞和中间神经元，改变它们的命运并在小鼠中产生颗粒神经元。而且，两个表达Nestin的祖细胞中的刺猬信号不仅对于颗粒神经元的补偿性补充而且对于缩放神经元和星形胶质细胞的数量都至关重要。因此，我们提供了对小脑电路形成鲁棒性的潜在机制的见解，并推测在其他大脑区域中祖细胞的适应性重编程在发育再生中起着比想象中更大的作用。