Neuronal fate determinants of adult olfactory bulb neurogenesis

Neuronal fate determinants of adult olfactory bulb neurogenesis
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DOI:
10.1038/nn1479
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发表时间:
2005-07-01
影响因子:
25
通讯作者:
Götz, M
Götz, M
中科院分区:
医学1区
文献类型:
--
作者:
Hack, MA;Saghatelyan, A;Götz, M

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哺乳动物的成年神经发生仅限于两个小区域,包括嗅球,其中GABA能和多巴胺能中间神经元在整个生命周期中新产生。然而,指导他们对一个特定的神经元表型的机制还不清楚。在这里,我们证明了双重作用的转录因子Pax6在产生神经元祖细胞,并在指导他们对多巴胺能肾小球周围表型在成年小鼠。我们提出了进一步的证据表明,多巴胺能肾小球周围神经元起源于一个独特的利基,吻侧迁移流,并较少来自前体的衬脑室区。成人前体细胞的这种区域化进一步得到转录因子Olig2的限制性表达的支持,Olig2指定了传递放大前体命运并反对Pax6的神经源性作用。总之,这些数据解释了外在和内在机制控制神经元的身份在成人神经发生。
Adult neurogenesis in mammals is restricted to two small regions, including the olfactory bulb, where GABAergic and dopaminergic interneurons are newly generated throughout the entire lifespan. However, the mechanisms directing them towards a specific neuronal phenotype are not yet understood. Here, we demonstrate the dual role of the transcription factor Pax6 in generating neuronal progenitors and also in directing them towards a dopaminergic periglomerular phenotype in adult mice. We present further evidence that dopaminergic periglomerular neurons originate in a distinct niche, the rostral migratory stream, and are fewer derived from precursors in the zone lining the ventricle. This regionalization of the adult precursor cells is further supported by the restricted expression of the transcription factor Olig2, which specifies transit-amplifying precursor fate and opposes the neurogenic role of Pax6. Together, these data explain both extrinsic and intrinsic mechanisms controlling neuronal identity in adult neurogenesis.