Dlx-dependent and -independent regulation of olfactory bulb interneuron differentiation
Dlx-dependent and -independent regulation of olfactory bulb interneuron differentiation
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DOI：
10.1523/jneurosci.5265-06.2007
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发表时间：
2007-03-21
影响因子：
5.3
通讯作者：
Rubenstein, John L. R.
中科院分区：
文献类型：
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作者：
Long, Jason E.;Garel, Sonia;Rubenstein, John L. R.
嗅球中间神经元的发育是一个复杂的多步骤过程，包括端脑腹侧的细胞特化、向嗅球的切向迁移和局部神经元的成熟。虽然有几个转录因子参与了这一过程，但它们如何或何时起作用仍有待阐明。在这里，我们探讨的机制，导致嗅球中间神经元缺陷Dlx 1和2（-/-）（远端少同源框1和2）和Mash 1（-/-）（哺乳动物achaete舒特同源1）突变体。我们提供的证据表明，Dlx 1和2和Mash 1调节这些细胞产生所需的平行分子途径，从而为嗅球发育的机制提供了新的见解。该分析还定义了与嗅球发育相关的不同解剖区域。最后，我们表明，Dlx 1和2所需的促进切向迁移到嗅球，可能通过调节ErbB 4（v-erb-红细胞白血病病毒癌基因同源物4），Robo 2（迂回同源物2），Slit 1（狭缝同源物1），PK 2（原动力蛋白2），这都已被证明在这种迁移中发挥重要作用的表达。
Olfactory bulb interneuron development is a complex multistep process that involves cell specification in the ventral telencephalon, tangential migration into the olfactory bulb, and local neuronal maturation. Although several transcription factors have been implicated in this process, how or when they act remains to be elucidated. Here we explore the mechanisms that result in olfactory bulb interneuron defects in Dlx1& 2(-/-)(distal-less homeobox 1 and 2) and Mash1(-/-) (mammalian achaete-schute homolog 1) mutants. We provide evidence that Dlx1& 2 and Mash1 regulate parallel molecular pathways that are required for the generation of these cells, thereby providing new insights into the mechanisms underlying olfactory bulb development. The analysis also defined distinct anatomical zones related to olfactory bulb development. Finally we show that Dlx1& 2 are required for promoting tangential migration to the olfactory bulb, potentially via regulating the expression of ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4), Robo2 (roundabout homolog 2), Slit1 (slit homolog 1), and PK2 (prokineticin 2), which have all been shown to play essential roles in this migration.