Genes expressed in Atoh1 neuronal lineages arising from the r1/isthmus rhombic lip.
Genes expressed in Atoh1 neuronal lineages arising from the r1/isthmus rhombic lip.
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DOI：
10.1016/j.gep.2011.03.007
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Fishell G
中科院分区：
文献类型：
--
作者：
Machold R;Klein C;Fishell G
在胚胎发生过程中，第四脑室的菱形唇是各种神经元群的生发起源，最终存在于脑干和小脑中。菱形唇神经发生需要bHLH转录因子Atoh1 (Math1)，并在神经管关闭后不久开始（E9.5）。在菱形球1 -峡区，菱形唇首先产生脑干和小脑深部神经元（E9.5-E12）， E12后产生颗粒细胞前体。虽然Atoh1的功能对于所有这些群体的确定都是必不可少的，但赋予早出生和晚出生的Atoh1谱系特定特性的下游遗传程序尚未得到很好的表征。我们对使用转基因标记策略从E14.5胚胎中纯化的表达Atoh1神经前体的早期和晚期出生队列的基因表达进行了比较微阵列分析。我们在每个Atoh1谱系中发现了新的转录因子、细胞表面分子和细胞周期调节因子，这些因子可能有助于它们独特的发育轨迹和细胞命运。特别是，我们的分析揭示了调控颗粒细胞前体的规范和增殖的遗传程序的新见解，颗粒细胞前体是大多数成神经管细胞瘤的假定起源细胞。
During embryogenesis, the rhombic lip of the fourth ventricle is the germinal origin of a diverse collection of neuronal populations that ultimately reside in the brainstem and cerebellum. Rhombic lip neurogenesis requires the bHLH transcription factor Atoh1 (Math1), and commences shortly after neural tube closure (E9.5). Within the rhombomere 1 – isthmus region, the rhombic lip first produces brainstem and deep cerebellar neurons (E9.5-E12), followed by granule cell precursors after E12. While Atoh1 function is essential for all of these populations to be specified, the downstream genetic programs that confer specific properties to early and late born Atoh1 lineages are not well characterized. We have performed a comparative microarray analysis of gene expression within early and later born cohorts of Atoh1 expressing neural precursors purified from E14.5 embryos using a transgenic labeling strategy. We identify novel transcription factors, cell surface molecules, and cell cycle regulators within each pool of Atoh1 lineages that likely contribute to their distinct developmental trajectories and cell fates. In particular, our analysis reveals new insights into the genetic programs that regulate the specification and proliferation of granule cell precursors, the putative cell of origin for the majority of medulloblastomas.
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