Id2 is required for specification of dopaminergic neurons during adult olfactory neurogenesis.

Id2 is required for specification of dopaminergic neurons during adult olfactory neurogenesis.
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DOI:
10.1523/jneurosci.3188-08.2008
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发表时间:
2008-12-24
期刊:
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子:
--
通讯作者:
Israel MA
Israel MA
中科院分区:
其他
文献类型:
--
作者:
Havrda MC;Harris BT;Mantani A;Ward NM;Paolella BR;Cuzon VC;Yeh HH;Israel MA

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了解成体神经干细胞的生物学对神经系统发育具有重要意义,并可能有助于我们了解神经退行性疾病及其治疗。我们的特点的过程中嗅神经发生在成年小鼠缺乏抑制剂的DNA结合2(Id 2)。我们发现一个减少嗅球含有颗粒和肾小球周围神经元的数量减少,多巴胺能肾小球周围神经元的明显缺乏。虽然没有检测到干细胞区室的缺陷,但Id 2 −/−突变小鼠中的迁移性成神经细胞在紊乱的吻侧迁移流中过早地经历了星形胶质细胞分化。此外,当在体外评估时,Id 2的损失导致神经祖细胞的增殖减少和Hes 1和Mash 1转录因子(已知的神经元分化的介质)的表达减少。这些数据支持一个新的作用,持续的Id 2表达迁移神经祖细胞介导的嗅觉多巴胺能神经元分化的成年动物。
Understanding the biology of adult neural stem cells has important implications for nervous system development and may contribute to our understanding of neurodegenerative disorders and their treatment. We have characterized the process of olfactory neurogenesis in adult mice lacking Inhibitor of DNA Binding 2 (Id2). We found a diminished olfactory bulb containing reduced numbers of granular and periglomerular neurons with a distinct paucity of dopaminergic periglomerular neurons. While no deficiency of the stem cell compartment was detectable, migrating neuroblasts in Id2−/− mutant mice prematurely undergo astroglial differentiation within a disorganized rostral migratory stream. Further, when evaluated in vitro loss of Id2 results in decreased proliferation of neural progenitors and decreased expression of the Hes1 and Mash1 transcription factors, known mediators of neuronal differentiation. These data support a novel role for sustained Id2 expression in migrating neural progenitors mediating olfactory dopaminergic neuronal differentiation in adult animals.