Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons

Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons
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DOI:
10.1523/jneurosci.1040-07.2007
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发表时间:
2007-05-30
影响因子:
5.3
通讯作者:
Fishell, Gord
Fishell, Gord
中科院分区:
医学1区
文献类型:
--
作者:
Balordi, Francesca;Fishell, Gord

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我们研究了在成体干细胞龛中去除Hedgehog信号的出生后后果。虽然出生时室管膜下区在缺乏Hedgehog信号传导的小鼠中表现正常,但到出生后第8天,室管膜下区严重受损,细胞死亡增加。此外,静止的B干细胞群和转运扩增的C细胞都在出生后耗尽.相比之下,A细胞群体早熟地扩增,大多数未能迁移到嗅球,并且最终也在出生后第30天耗尽。体外和体内分析表明,这种迁移失败是非自主信号传导的结果,可能是由A细胞中Slit 1配体的减少引起的。这些结果表明,Hedgehog信号传导是维持B和C细胞群所必需的,并且间接地是由成体干细胞龛产生的神经元的迁移所必需的。
We examined the postnatal consequences of removing Hedgehog signaling within the adult stem cell niche. Although at birth the subventricular zone appears normal in mice lacking Hedgehog signaling, by postnatal day 8 it is greatly impaired, and cell death is increased. In addition, both the quiescent B stem cell population and transit- amplifying C cells become depleted postnatally. In contrast, the A cell population expands precociously, mostly fails to migrate to the olfactory bulbs, and is ultimately also depleted by postnatal day 30. In vitro and in vivo analyses demonstrate that this failure in migration is a result of nonautonomous signaling, possibly caused by a reduction in Slit1 ligand in A cells. These results suggest that Hedgehog signaling is required for the maintenance of the B and C cell populations and indirectly for the migration of the neurons that are generated from the adult stem cell niche.