Zac1 plays a key role in the development of specific neuronal subsets in the mouse cerebellum.
Zac1 plays a key role in the development of specific neuronal subsets in the mouse cerebellum.
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DOI：
10.1186/1749-8104-6-25
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发表时间：
2011-05-18
影响因子：
3.6
通讯作者：
Hawkes R
中科院分区：
文献类型：
--
作者：
Chung SH;Marzban H;Aldinger K;Dixit R;Millen K;Schuurmans C;Hawkes R
小脑由多种神经元亚型组成。在这里，我们已经使用了一个候选人的方法来识别Zac 1，一个肿瘤抑制基因编码的锌指转录因子，作为一个新的球员在转录网络所需的发展的一个特定的子集小脑核和一个人口的高尔基体细胞在小脑皮质。我们发现Zac 1在发育中的小脑中具有复杂的表达谱，包括两个增殖的祖细胞群体;小脑脑室区和覆盖小脑后小叶IX和X的外部颗粒层。Zac 1也在一些有丝分裂后的小脑神经元中表达，包括小脑内侧核中的GABA能中间神经元的子集。值得注意的是，小脑核中的GABA能中间神经元来源于小脑脑室区，其中Zac 1也表达，这与这两个Zac 1+群体之间的谱系关系一致。Zac 1也在后蚓部的一小部分细胞中表达，包括一些神经颗粒蛋白免疫反应（NG+）高尔基体细胞，基于短期出生日期，这些细胞来自EGL，其中Zac 1也表达。然而，小脑皮质中的Zac 1+细胞和NG+高尔基体细胞也显示出独特的特性，因为它们是在不同的时间窗内产生的，尽管它们是重叠的。最后，与Zac 1的表达谱相一致，在Zac 1基因敲除小鼠的小脑中发现了两个明显的异常：小脑内侧核，而不是其他核，大小显著减少;与野生型同窝小鼠相比，小脑小叶IX中高尔基体细胞的数量减少了约60%。这里提出的数据表明，肿瘤抑制基因Zac 1是在一个复杂的方式表达在发展中的小脑，包括在两个分裂的祖细胞群体和特定的有丝分裂后的神经元，包括高尔基体细胞和GABA能神经元的内侧核，这需要Zac 1为他们的分化。因此，我们得出结论，Zac 1是一个重要的调节正常小脑发育，增加了一个新的转录调节因子参与产生神经元的多样性在发展中的小脑越来越多的名单。
The cerebellum is composed of a diverse array of neuronal subtypes. Here we have used a candidate approach to identify Zac1, a tumor suppressor gene encoding a zinc finger transcription factor, as a new player in the transcriptional network required for the development of a specific subset of cerebellar nuclei and a population of Golgi cells in the cerebellar cortex. We found that Zac1 has a complex expression profile in the developing cerebellum, including in two proliferating progenitor populations; the cerebellar ventricular zone and the external granular layer overlying posterior cerebellar lobules IX and X. Zac1 is also expressed in some postmitotic cerebellar neurons, including a subset of GABAergic interneurons in the medial cerebellar nuclei. Notably, GABAergic interneurons in the cerebellar nuclei are derived from the cerebellar ventricular zone, where Zac1 is also expressed, consistent with a lineage relationship between these two Zac1+ populations. Zac1 is also expressed in a small subset of cells in the posterior vermis, including some neurogranin-immunoreactive (NG+) Golgi cells, which, based on short-term birthdating, are derived from the EGL, where Zac1 is also expressed. However, Zac1+ cells and NG+ Golgi cells in the cerebellar cortex also display unique properties, as they are generated within different, albeit overlapping, time windows. Finally, consistent with the expression profile of Zac1, two conspicuous abnormalities were found in the cerebellum of Zac1 null mice: the medial cerebellar nuclei, and not the others, were significantly reduced in size; and the number of Golgi cells in cerebellar lobule IX was reduced by approximately 60% compared to wild-type littermates. The data presented here indicate that the tumor suppressor gene Zac1 is expressed in a complex fashion in the developing cerebellum, including in two dividing progenitor populations and in specific subsets of postmitotic neurons, including Golgi cells and GABAergic neurons in the medial nuclei, which require Zac1 for their differentiation. We thus conclude that Zac1 is a critical regulator of normal cerebellar development, adding a new transcriptional regulator to the growing list of factors involved in generating neuronal diversity in the developing cerebellum.