RhoA is dispensable for axon guidance of sensory neurons in the mouse dorsal root ganglia.

RhoA is dispensable for axon guidance of sensory neurons in the mouse dorsal root ganglia.
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DOI:
10.3389/fnmol.2012.00067
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发表时间:
2012
影响因子:
4.8
通讯作者:
Yoshida Y
Yoshida Y
中科院分区:
医学2区
文献类型:
--
作者:
Leslie JR;Imai F;Zhou X;Lang RA;Zheng Y;Yoshida Y

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RhoA是Rho家族小GTP酶的一员,已被证明在轴突引导中发挥重要作用。然而,到目前为止,RhoA在体内轴突引导事件中的生理功能还没有在动物中从遗传学上确定。在这里,我们发现RhoA mRNA在发育中的小鼠背根神经节(DRG)中由感觉神经元强烈表达。我们已经在Wnt1-Cre驱动程序下使用RhoA-Floking小鼠删除了DRG感觉神经元中的RhoA,其中Cre在感觉神经元中强烈表达。在RhoAf/f;Wnt1-Cre小鼠中,感觉神经元的外周投射正常,皮肤或本体感觉感觉神经元的中枢投射没有可检测到的缺陷。此外,使用RhoAf/f;Wnt1-Cre胚胎的DRG外植体与表达信号素3A(Sema3A)的293T细胞进行的共同培养试验表明,RhoA不是Sema3A介导的感觉神经元轴突排斥所必需的。RhoC是一个密切相关的家族成员,在RhoA缺乏的感觉神经元中表达增加,可能在这一背景下起到代偿作用。综上所述,这些遗传学研究表明,RhoA对于DRG中感觉神经元的外周和中枢投射是必不可少的。
RhoA, a member of the Rho family small GTPases, has been shown to play important roles in axon guidance. However, to date, the physiological function of RhoA in axon guidance events in vivo has not been determined genetically in animals. Here we show that RhoA mRNA is strongly expressed by sensory neurons in the developing mouse dorsal root ganglia (DRG). We have deleted RhoA in sensory neurons of the DRG using RhoA-floxed mice under the Wnt1-Cre driver in which Cre is strongly expressed in sensory neurons. Peripheral projections of sensory neurons appear normal and there are no detectable defects in the central projections of either cutaneous or proprioceptive sensory neurons in RhoAf/f; Wnt1-Cre mice. Furthermore, a co-culture assay using DRG explants from RhoAf/f; Wnt1-Cre embryos, and 293T cells expressing semaphorin3A (Sema3A) reveals that RhoA is not required for Sema3A-mediated axonal repulsion of sensory neurons. Expression of RhoC, a closely related family member, is increased in RhoA-deficient sensory neurons and may play a compensatory role in this context. Taken together, these genetic studies demonstrate that RhoA is dispensable for peripheral and central projections of sensory neurons in the DRG.
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