Runx1 promotes neuronal differentiation in dorsal root ganglion
Runx1 promotes neuronal differentiation in dorsal root ganglion
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DOI：
10.1016/j.mcn.2011.08.009
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发表时间：
2012-01-01
影响因子：
3.5
通讯作者：
Shiga, Takashi
中科院分区：
文献类型：
--
作者：
Kobayashi, Azusa;Senzaki, Kouji;Shiga, Takashi
转录因子Runx 1通过在胚胎晚期和出生后早期抑制TrkA和降钙素基因相关肽（CGRP）表达并激活Ret表达来控制肽能和非肽能伤害性背根神经节（DRG）神经元的细胞类型特化（Chen et al.，2006 b;克雷默等人，2006; Yoshikawa等人，2007年）。由于Runx 1在DRG的早期发育阶段表达，我们研究了Runx 1在DRG细胞增殖和神经元分化中的作用。我们使用转基因Runx 1缺陷型（Runx 1（-/-）：：Tg）小鼠，其通过在加塔-1启动子控制下在造血细胞中选择性表达Runx 1而从早期胚胎致死中被拯救。我们发现TrkA表达（TrkA（+））DRG神经元在胚胎第（E）12.5天减少，与先前的研究相反，先前的研究显示在Runx 1（-/-）：：Tg小鼠中TrkA（+）DRG神经元在E17.5增加（Yoshikawa et al.，2007年）。在E12.5时，Runx 1（-/-）：：Tg小鼠中表达神经元标记物Hu、NeuN和Islet 1的DRG神经元数量也减少，表明这些小鼠中的神经元分化受到抑制。BrdU/IDU细胞周期分析显示，Runx 1（-/-）：：Tg小鼠在E12. 5时，S期和G2/M期的DRG细胞数量增加，而Runx 1（+/+）：：Tg和Runx 1（-/-）：：Tg小鼠的S期长度没有变化，表明Runx 1负调控胚胎早期DRG祖细胞亚群的增殖。Hes 1是神经元分化的负调节因子（Ishibashi等人，1995; Tomita等人，1996），并且我们发现在E12.5时Runx 1（-/-）：：Tg小鼠中Hes 1（+）DRG细胞的数量增加。总之，本研究提示Runx 1通过抑制Hes 1在胚胎早期的表达而激活DRG细胞亚群的神经元分化。(C)2011 Elsevier Inc. All rights reserved.
Transcription factor Runx1 controls the cell type specification of peptidergic and nonpeptidergic nociceptive dorsal root ganglion (DRG) neurons by repressing TrkA and calcitonin gene-related peptide (CGRP) expression and activating Ret expression during late embryonic and early postnatal periods (Chen et al., 2006b; Kramer et al., 2006; Yoshikawa et al., 2007). Because Runx1 is expressed in DRG from early developmental stages, we examined the roles of Runx1 in the proliferation and the neuronal differentiation of DRG cells. We used transgenic Runx1-deficient (Runx1(-/-)::Tg) mice which are rescued from early embryonic lethality by selective expression of Runx1 in hematopoietic cells under the control of GATA-1 promoter. We found that TrkA-expressing (TrkA(+)) DRG neurons were decreased at embryonic day (E) 12.5 in contrast to the previous study showing that TrkA(+) DRG neurons were increased at E17.5 in Runx1(-/-)::Tg mice (Yoshikawa et al., 2007). The number of DRG neurons which express neuronal markers Hu, NeuN and Islet1 was also reduced in Runx1(-/-)::Tg mice at E12.5, suggesting that the neuronal differentiation was suppressed in these mice. The cell cycle analysis using BrdU/IDU revealed that the number of DRG cells in S-phase and G2/M-phase was increased in Runx1(-/-) ::Tg mice at E12.5, while the length of S-phase was not changed between Runx1(+/+)::Tg and Runx1(-/-) ::Tg mice, suggesting that Runx1 negatively controls the proliferation of DRG progenitor cell subpopulation in early embryonic period. Hes1 is a negative regulator of neuronal differentiation (Ishibashi et al., 1995; Tomita et al., 1996), and we found that the number of Hes1(+) DRG cells was increased in Runx1(-/-)::Tg mice at E12.5. In summary, the present study suggests a novel function that Runx1 activates the neuronal differentiation of DRG cell subpopulation through the repression of Hes1 expression in early embryonic period. (C) 2011 Elsevier Inc. All rights reserved.