The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons
The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons
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DOI：
10.1093/emboj/cdf370
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发表时间：
2002-07-01
期刊：
影响因子：
11.4
通讯作者：
Groner, Y
中科院分区：
文献类型：
--
作者：
Levanon, D;Bettoun, D;Groner, Y
RUNX转录因子是主要发育途径中谱系特异性基因表达的重要调节因子。最近，我们证明Runx 3在发育中的颅和背根神经节（DRG）中高度表达。在这里，我们报告说，在背根神经节，Runx 3是专门表达在一个子集的神经元，酪氨酸激酶受体C（TrkC）本体感受神经元。我们发现Runx 3缺陷小鼠由于脊髓内传入神经和运动神经元之间的单突触连接中断而发生严重的肢体共济失调。我们证明，缺陷的根本原因是DRG本体感受神经元的损失，反映了TrkC，小白蛋白和β-半乳糖苷酶阳性细胞的数量减少。因此，Runx 3是神经源性TrkC神经元特异性转录因子。在缺乏TrkC的情况下，DRG中的TrkC神经元不能存活足够长的时间以将其轴突延伸到靶细胞，导致缺乏连接和共济失调。这些数据为DRG的神经发生提供了新的遗传学见解，并可能有助于阐明人类体感相关共济失调的分子机制。
The RUNX transcription factors are important regulators of linage-specific gene expression in major developmental pathways. Recently, we demonstrated that Runx3 is highly expressed in developing cranial and dorsal root ganglia (DRGs). Here we report that within the DRGs, Runx3 is specifically expressed in a subset of neurons, the tyrosine kinase receptor C (TrkC) proprioceptive neurons. We show that Runx3-deficient mice develop severe limb ataxia due to disruption of monosynaptic connectivity between intra spinal afferents and motoneurons. We demonstrate that the underlying cause of the defect is a loss of DRG proprioceptive neurons, reflected by a decreased number of TrkC-, parvalbumin- and beta-galactosidase-positive cells. Thus, Runx3 is a neurogenic TrkC neuron-specific transcription factor. In its absence, TrkC neurons in the DRG do not survive long enough to extend their axons toward target cells, resulting in lack of connectivity and ataxia. The data provide new genetic insights into the neurogenesis of DRGs and may help elucidate the molecular mechanisms underlying somatosensory-related ataxia in humans.