Rac1 and Rac3 GTPases regulate the development of hilar mossy cells by affecting the migration of their precursors to the hilus.
Rac1 and Rac3 GTPases regulate the development of hilar mossy cells by affecting the migration of their precursors to the hilus.
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DOI：
10.1371/journal.pone.0024819
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
de Curtis I
中科院分区：
文献类型：
--
作者：
Pennucci R;Tavano S;Tonoli D;Gualdoni S;de Curtis I
我们之前已经证明，在神经元发育过程中，Rac1和Rac3 gtpase基因的双重缺失会影响海马回路紊乱的发育后期事件，从而导致癫痫表型。这些影响包括苔藓细胞的缺陷，苔藓细胞是门部兴奋性神经元的主要种类。在这里，我们研究了影响两种Rac gtpase缺失小鼠海马背侧门状苔藓细胞损失的机制。定量显示，在出生后第8天，这些细胞被背门的特定标记物识别后不久，苔藓细胞的损失就很明显了。对照小鼠和双突变小鼠的门区对比分析显示，双突变小鼠的突触发生受到影响，来自齿状颗粒细胞的突触前输入明显减少。我们发现，对照组和双敲除小鼠的海马细胞凋亡同样低。在胚胎12.5天用溴脱氧尿苷标记海马原基中神经元前体细胞的增殖没有明显差异，而发育中的门孔中溴脱氧尿苷标记细胞数量的差异表明双敲除小鼠未成熟的、发育中的苔藓细胞在大脑中的迁移存在缺陷。综上所述，我们的数据表明Rac1和Rac3 gtpase参与了门侧苔藓细胞的正常发育，并表明它们通过阻止苔藓细胞前体到达门侧背参与了苔藓细胞迁移的调控。
We have previously shown that double deletion of the genes for Rac1 and Rac3 GTPases during neuronal development affects late developmental events that perturb the circuitry of the hippocampus, with ensuing epileptic phenotype. These effects include a defect in mossy cells, the major class of excitatory neurons of the hilus. Here, we have addressed the mechanisms that affect the loss of hilar mossy cells in the dorsal hippocampus of mice depleted of the two Rac GTPases. Quantification showed that the loss of mossy cells was evident already at postnatal day 8, soon after these cells become identifiable by a specific marker in the dorsal hilus. Comparative analysis of the hilar region from control and double mutant mice revealed that synaptogenesis was affected in the double mutants, with strongly reduced presynaptic input from dentate granule cells. We found that apoptosis was equally low in the hippocampus of both control and double knockout mice. Labelling with bromodeoxyuridine at embryonic day 12.5 showed no evident difference in the proliferation of neuronal precursors in the hippocampal primordium, while differences in the number of bromodeoxyuridine-labelled cells in the developing hilus revealed a defect in the migration of immature, developing mossy cells in the brain of double knockout mice. Overall, our data show that Rac1 and Rac3 GTPases participate in the normal development of hilar mossy cells, and indicate that they are involved in the regulation of the migration of the mossy cell precursor by preventing their arrival to the dorsal hilus.
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影响因子：
7.8
作者：
Albertinazzi, C;Gilardelli, D;de Curtis, I
通讯作者：
de Curtis, I
DOI：
10.1523/jneurosci.3612-08.2008
发表时间：
2008-11-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Larimer P;Strowbridge BW
通讯作者：
Strowbridge BW
影响因子：
2.5
作者：
ALTMAN, J;BAYER, SA
通讯作者：
BAYER, SA
影响因子：
2.9
作者：
Fujise, N;Kosaka, T
通讯作者：
Kosaka, T
影响因子：
5.6
作者：
Blümcke, I;Suter, B;Wiestler, OD
通讯作者：
Wiestler, OD