The zinc finger transcription factor Sp8 regulates the generation and diversity of olfactory bulb interneurons
The zinc finger transcription factor Sp8 regulates the generation and diversity of olfactory bulb interneurons
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DOI：
10.1016/j.neuron.2006.01.018
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发表时间：
2006-02-16
期刊：
影响因子：
16.2
通讯作者：
Campbell, K
中科院分区：
文献类型：
--
作者：
Waclaw, RR;Allen, ZJ;Campbell, K
调节嗅球中间神经元的产生和多样性的分子机制仍然知之甚少。除了肾小球层中的 GABA 能/多巴胺能亚型外，不存在有关其他亚型产生的信息。在这里，我们发现最近发现的锌指转录因子 Sp8 在神经源性区域中表达，该区域在胚胎和出生后时间点产生嗅球中间神经元，并且在肾小球层的钙结合蛋白表达和 GABA 能/非多巴胺能中间神经元中保持表达。胚胎腹侧端脑中 Sp8 的条件性失活揭示了这些中间神经元亚型正常生成的必要条件。 Sp8条件突变体表现出外侧神经节隆起和吻端迁移流内细胞死亡的增加。此外，突变的神经母细胞/中间神经元被错误指定，并在嗅球中表现出异常的迁移模式，表明Sp8通过调节神经母细胞/中间神经元的存活、迁移和分子规范来促进嗅球中间神经元的多样性。
The molecular mechanisms that regulate the production and diversity of olfactory bulb interneurons remain poorly understood. With the exception of the GABAergic/dopaminergic subtype in the glomerular layer, no information exists concerning the generation of the other subtypes. Here we show that the recently identified zinc finger transcription factor Sp8 is expressed in neurogenic regions, which give rise to olfactory bulb interneurons at embryonic and postnatal time points and remains expressed in the calretinin-expressing and GABAergic/nondopaminergic interneurons of the glomerular layer. Conditional inactivation of Sp8 in the embryonic ventral telencephalon reveals a requirement for the normal generation of these interneuron subtypes. Sp8 conditional mutants exhibit an increase in cell death within the lateral ganglionic eminence and rostral migratory stream. Moreover, mutant neuroblasts/interneurons are misspecified and display abnormal migration patterns in the olfactory bulb, indicating that Sp8 contributes to olfactory bulb interneuron diversity by regulating the survival, migration, and molecular specification of neuroblasts/interneurons.