Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb

Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb
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DOI:
10.1523/jneurosci.1435-05.2005
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发表时间:
2005-07-27
影响因子:
5.3
通讯作者:
Alvarez-Buylla, A
Alvarez-Buylla, A
中科院分区:
医学1区
文献类型:
--
作者:
Kohwi, M;Osumi, N;Alvarez-Buylla, A

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室管膜下区(SVZ)在人的一生中产生不同的嗅球(OB)中间神经元亚类。关于控制不同类型的中间神经元产生的分子机制知之甚少。在这里,我们发现,大多数增殖的成人SVZ祖细胞表达的转录因子Pax 6,但只有一小部分迁移的神经母细胞和新的OB中间神经元来自这些祖细胞保留Pax 6的表达。为了阐明Pax 6在OB神经发生中的细胞自主作用,我们将Pax 6突变型小眼(Pax 6(Sey/ Sey))小鼠背外侧神经节隆起的表达绿色荧光蛋白的胚胎前脑祖细胞移植到成年野生型小鼠的SVZ中. Pax 6(Sey/ Sey)祖细胞产生能够迁移到OB的成神经细胞,但不能产生多巴胺能肾小球周围和表面颗粒细胞。有趣的是,表面颗粒神经元也表达酪氨酸羟化酶的mRNA,酪氨酸羟化酶是多巴胺合成的限速酶.我们的数据显示SVZ神经母细胞是异质的,并且Pax 6以细胞自主的方式被需要用于多巴胺能谱系中的细胞的产生。
The subventricular zone ( SVZ) produces different subclasses of olfactory bulb ( OB) interneurons throughout life. Little is known about the molecular mechanisms controlling the production of different types of interneurons. Here we show that most proliferating adult SVZ progenitors express the transcription factor Pax6, but only a small subpopulation of migrating neuroblasts and new OB interneurons derived from these progenitors retains Pax6 expression. To elucidate the cell- autonomous role of Pax6 in OB neurogenesis, we transplanted green fluorescent protein- expressing embryonic forebrain progenitors of the dorsal lateral ganglionic eminence from Pax6 mutant Small Eye ( Pax6(Sey/ Sey)) mice into the SVZ of adult wild- type mice. Pax6(Sey/ Sey) progenitors produce neuroblasts capable of migrating into the OB but fail to generate dopaminergic periglomerular and superficial granule cells. Interestingly, superficial granule neurons also express mRNA for tyrosine hydroxylase, the rate- limiting enzyme in dopamine synthesis. Our data show that SVZ neuroblasts are heterogeneous and that Pax6 is required in a cell- autonomous manner for the production of cells in the dopaminergic lineage.