Wnt signaling and its downstream target N-myc regulate basal progenitors in the developing neocortex

Wnt signaling and its downstream target N-myc regulate basal progenitors in the developing neocortex
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DOI:
10.1242/dev.046417
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发表时间:
2010-04-01
期刊:
影响因子:
4.6
通讯作者:
Gotoh, Yukiko
Gotoh, Yukiko
中科院分区:
生物学2区
文献类型:
--
作者:
Kuwahara, Atsushi;Hirabayashi, Yusuke;Gotoh, Yukiko

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基底祖细胞(也称为非表面分裂或中间祖细胞)已被提议通过扩大致力于神经元命运的细胞来调节新皮质发育期间神经元的数量,尽管控制该群体的信号在很大程度上仍然未知。在这里,我们证明 N-myc 介导 Wnt 信号传导在促进神经元命运定型和体外神经前体细胞增殖中的功能。 Wnt 信号传导和 N-myc 也有助于体内基础祖细胞的产生。 β-连环蛋白(Wnt 信号通路的一个组成部分)或 N-myc 的稳定形式的表达增加了新皮质基底祖细胞的数量,而 N-myc 基因的条件性删除则减少了这些祖细胞,并可能导致新皮质神经元的数量。这些结果表明,通过 N-myc 的 Wnt 信号传导对于控制发育中的新皮质中的神经元数量至关重要。
Basal progenitors (also called non-surface dividing or intermediate progenitors) have been proposed to regulate the number of neurons during neocortical development through expanding cells committed to a neuronal fate, although the signals that govern this population have remained largely unknown. Here, we show that N-myc mediates the functions of Wnt signaling in promoting neuronal fate commitment and proliferation of neural precursor cells in vitro. Wnt signaling and N-myc also contribute to the production of basal progenitors in vivo. Expression of a stabilized form of beta-catenin, a component of the Wnt signaling pathway, or of N-myc increased the numbers of neocortical basal progenitors, whereas conditional deletion of the N-myc gene reduced these and, as a likely consequence, the number of neocortical neurons. These results reveal that Wnt signaling via N-myc is crucial for the control of neuron number in the developing neocortex.