Runx1 selectively regulates cell fate specification and axonal projections of dorsal root ganglion neurons
Runx1 selectively regulates cell fate specification and axonal projections of dorsal root ganglion neurons
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DOI：
10.1016/j.ydbio.2006.12.007
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发表时间：
2007-03-15
影响因子：
2.7
通讯作者：
Shiga, Takashi
中科院分区：
文献类型：
--
作者：
Yoshikawa, Masaaki;Senzaki, Kouji;Shiga, Takashi
Runx 1缺陷小鼠在胚胎第11.5天左右由于造血功能受损而死亡。这种早期死亡阻止了Runx 1在感觉神经节发育中作用的分析。为了克服早期胚胎致死性，我们采用了一种新的方法来利用转基因Runx 1缺陷小鼠，其中造血细胞通过加塔-1启动子控制下的Runx 1表达来选择性地拯救。在Runx 1缺陷小鼠中，背根神经节（DRG）神经元的总数增加，可能是因为DRG祖细胞的增殖活性增加和凋亡减少。在突变的DRG中，TrkA阳性神经元和肽能神经元增多，而c-ret阳性神经元减少。轴突的预测也改变了，在CGRP阳性轴突的中央和外周的预测增加。在脊髓背角，CGRP阳性轴突的投射从正常终末区I/IIo扩展到更深层Ili。我们的研究结果表明，Runx 1参与皮肤神经元的细胞命运规范，以及他们的预测中央和外周目标。(c)2006爱思唯尔公司All rights reserved.
Runx1-deficient mice die around embryonic day 11.5 due to impaired hematopoiesis. This early death prevents the analysis of the role of Runx1 in the development of sensory ganglia. To overcome the early embryonic lethality, we adopted a new approach to utilize transgenic Runx1-deficient mice in which hematopoietic cells are selectively rescued by Runx1 expression under the control of GATA-1 promoter. In Runx1-deficient mice, the total number of dorsal root ganglion (DRG) neurons was increased, probably because of an increased proliferative activity of DRG progenitor cells and decreased apoptosis. in the mutant DRG, TrkA-positive neurons and peptidergic neurons were increased, while c-ret-positive neurons were decreased. Axonal projections were also altered, in that both central and peripheral projections of CGRP-positive axons were increased. In the dorsal horn of the spinal cord, projections of CGRP-positive axons expanded to the deeper layer, Ili, from the normal terminal area, I/IIo. Our results suggest that Runx1 is involved in the cell fate specification of cutaneous neurons, as well as their projections to central and peripheral targets. (c) 2006 Elsevier Inc. All rights reserved.