Brn3a regulates the transition from neurogenesis to terminal differentiation and represses non-neural gene expression in the trigeminal ganglion.
Brn3a regulates the transition from neurogenesis to terminal differentiation and represses non-neural gene expression in the trigeminal ganglion.
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DOI：
10.1002/dvdy.22145
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发表时间：
2009-12
影响因子：
2.5
通讯作者：
Turner, Eric E.
中科院分区：
文献类型：
--
作者：
Lanier, Jason;Dykes, Iain M.;Nissen, Stephanie;Eng, S. Raisa;Turner, Eric E.
POU结构域转录因子Brn 3a在神经轴的所有水平的发育中的感觉神经元中表达，包括三叉神经节、后脑感觉神经节和背根神经节。从E11.5到E13.5，三叉神经节中全球基因表达的变化反映了早期神经基因的抑制，从细胞周期中退出，以及感觉功能的决定性标志物表达的启动。大多数这些发育变化在Brn 3a基因敲除小鼠的三叉神经节中受到干扰。在E13.5，Brn 3a −/−三叉神经元不能抑制一系列在E11.5高度表达的发育调节因子，并且通常随着发育的进展而下调，也不能适当地激活一组确定的感觉基因。值得注意的是，发育中的Brn 3a −/−三叉神经元也异位表达与心脏和/或颅中胚层发育相关的多种调控基因，尽管最终的肌源性程序没有被激活。这些基因中的大多数在Brn 3a缺失小鼠的背根神经节中不异位表达，这可能是由于在脊髓水平的冗余抑制机制。这些结果强调了基因抑制在调节神经元发育中的重要性，以及在确定发育基因调控程序中需要无偏筛选。
The POU-domain transcription factor Brn3a is expressed in developing sensory neurons at all levels of the neural axis, including the trigeminal ganglion, hindbrain sensory ganglia, and dorsal root ganglia. Changes in global gene expression in the trigeminal ganglion from E11.5 to E13.5 reflect the repression of early neurogenic genes, exit from the cell cycle, and initiation of the expression of definitive markers of sensory function. A majority of these developmental changes are perturbed in the trigeminal ganglia of Brn3a knockout mice. At E13.5, Brn3a−/− trigeminal neurons fail to repress a battery of developmental regulators which are highly expressed at E11.5 and are normally down-regulated as development progresses, and also fail to appropriately activate a set of definitive sensory genes. Remarkably, developing Brn3a−/− trigeminal neurons also ectopically express multiple regulatory genes associated with cardiac and/or cranial mesoderm development, although definitive myogenic programs are not activated. The majority of these genes are not ectopically expressed in the dorsal root ganglia of Brn3a null mice, perhaps due to redundant mechanisms of repression at spinal levels. These results underscore the importance of gene repression in regulating neuronal development, and the need for unbiased screens in the determination of developmental gene regulatory programs.
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