Balordi Francesca, Fishell Gord
Smilow Neuroscience Program and the Department of Cell Biology, Smilow Research Center, New York University School of Medicine, New York, New York 10016, USA.
J Neurosci. 2007 May 30;27(22):5936-47. doi: 10.1523/JNEUROSCI.1040-07.2007.
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.
我们研究了在成体干细胞生态位中去除刺猬信号通路后对出生后产生的影响。尽管在出生时,缺乏刺猬信号通路的小鼠的脑室下区看起来正常,但到出生后第8天,该区域受到严重损害,细胞死亡增加。此外,静止的B干细胞群和过渡扩增的C细胞在出生后都会减少。相比之下,A细胞群过早扩张,大部分未能迁移到嗅球,最终在出生后第30天也会减少。体外和体内分析表明,这种迁移失败是由非自主信号传导导致的,可能是由于A细胞中Slit1配体减少所致。这些结果表明,刺猬信号通路对于维持B和C细胞群是必需的,并且间接影响从成体干细胞生态位产生的神经元的迁移。