A Dlx2-and Pax6-dependent transcriptional code for periglomerular neuron specification in the adult olfactory bulb
A Dlx2-and Pax6-dependent transcriptional code for periglomerular neuron specification in the adult olfactory bulb
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DOI：
10.1523/jneurosci.0700-08.2008
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发表时间：
2008-06-18
影响因子：
5.3
通讯作者：
Goetz, Magdalena
中科院分区：
文献类型：
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作者：
Brill, Monika S.;Snapyan, Marina;Goetz, Magdalena
不同的嗅球（OB）中间神经元被认为是指定的，这取决于它们起源于侧脑室壁内衬的不同亚区，但区域特异性转录因子（TF）在OB中间神经元多样性产生中的作用仍然知之甚少。尽管在胚胎发育过程中，Dlx家族的TF在腹侧端脑的模式化和神经发生中起着至关重要的作用，但它们在成人神经发生中的作用尚未得到解决。在这里，我们表明，在成年人的大脑中，Dlx 1和Dlx 2表达的祖细胞的外侧，而不是背侧室管膜下区（SEZ），从而表现出惊人的区域特异性。使用逆转录病毒载体检查Dlx2的功能，在一个细胞自主的方式，我们表明，这种TF是必要的，几乎所有的OB中间神经元产生的外侧经济特区的神经发生。除了其在一般神经发生中的功能之外，Dlx2还在OB中的神经元亚型特化中发挥关键作用，促进成人出生的肾小球周围神经元（PGN）向多巴胺能命运的特化。引人注目的是，Dlx2需要与Pax6相互作用，因为Pax6缺失阻断Dlx2介导的PGN特化。因此，Dlx2通过首先指导来自成人前体的一般神经发生并随后与Pax6结合指定PGN亚型来行使双重功能。
Distinct olfactory bulb (OB) interneurons are thought to become specified depending on from which of the different subregions lining the lateral ventricle wall they originate, but the role of region-specific transcription factors (TFs) in the generation of OB interneurons diversity is still poorly understood. Despite the crucial roles of the Dlx family of TFs for patterning and neurogenesis in the ventral telencephalon during embryonic development, their role in adult neurogenesis has not yet been addressed. Here we show that in the adult brain, Dlx 1 and Dlx2 are expressed in progenitors of the lateral but not the dorsal subependymal zone (SEZ), thus exhibiting a striking regional specificity. Using retroviral vectors to examine the function of Dlx2 in a cell-autonomous manner, we demonstrate that this TF is necessary for neurogenesis of virtually all OB interneurons arising from the lateral SEZ. Beyond its function in generic neurogenesis, Dlx2 also plays a crucial role in neuronal subtype specification in the OB, promoting specification of adult-born periglomerular neurons (PGNs) toward a dopaminergic fate. Strikingly, Dlx2 requires interaction with Pax6, because Pax6 deletion blocks Dlx2-mediated PGN specification. Thus, Dlx2 wields a dual function by first instructing generic neurogenesis from adult precursors and subsequently specifying PGN subtypes in conjunction with Pax6.