Intrinsically determined cell death of developing cortical interneurons.
Intrinsically determined cell death of developing cortical interneurons.
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作者：
皮层抑制回路是由gaba能中间神经元形成的，这是一种细胞群，起源于远离大脑皮层的胚胎前脑腹侧。考虑到它们遥远的发育起源，皮层中间神经元的数量最终是如何确定的，这是一个有趣的问题。神经营养假说提出的一种可能性是，皮层中间神经元产生过多，然后随着它们迁移到皮层，多余的中间神经元通过对外部来源的营养信号的竞争而被淘汰。在这里，我们描述了小鼠皮质中间神经元在体内、体外和移植后的发育细胞死亡。我们发现40%的皮质中间神经元在出生后通过Bax- （Bcl-2相关的X-）依赖性凋亡被消除。当在体外培养或移植到皮层时，中间神经元前体的细胞年龄与内源性中间神经元在正常发育过程中死亡的细胞年龄相似。值得注意的是，在移植大小变化了200倍的移植群体中，有一定比例的移植群体发生了细胞死亡。TrkB（原肌球蛋白激酶受体B）是中枢神经系统（CNS）神经元表达的主要神经营养因子受体，其细胞自主破坏不影响移植神经元的死亡。移植使皮质中间神经元数量增加了35%，但抑制性突触事件的频率不随移植中间神经元数量的增加而增加。总之，我们的研究结果表明，中间神经元细胞的死亡是内在决定的，要么是细胞自主的，要么是通过来自其他中间神经元的生存信号的群体自主竞争。
Cortical inhibitory circuits are formed by GABAergic interneurons, a cell population that originates far from the cerebral cortex in the embryonic ventral forebrain. Given their distant developmental origins, it is intriguing how the number of cortical interneurons is ultimately determined. One possibility, suggested by the neurotrophic hypothesis, is that cortical interneurons are overproduced, and then following their migration into cortex, excess interneurons are eliminated through a competition for extrinsically derived trophic signals. Here we have characterized the developmental cell death of mouse cortical interneurons in vivo, in vitro, and following transplantation. We found that 40% of developing cortical interneurons were eliminated through Bax- (Bcl-2 associated X-) dependent apoptosis during postnatal life. When cultured in vitro or transplanted into the cortex, interneuron precursors died at a cellular age similar to that at which endogenous interneurons died during normal development. Remarkably, over transplant sizes that varied 200-fold, a constant fraction of the transplanted population underwent cell death. The death of transplanted neurons was not affected by the cell-autonomous disruption of TrkB (tropomyosin kinase receptor B), the main neurotrophin receptor expressed by central nervous system (CNS) neurons. Transplantation expanded the cortical interneuron population by up to 35%, but the frequency of inhibitory synaptic events did not scale with the number of transplanted interneurons. Together, our findings indicate that interneuron cell death is intrinsically determined, either cell-autonomously, or through a population-autonomous competition for survival signals derived from other interneurons.
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影响因子：
56.9
作者：
SAUNDERS, JW
通讯作者：
SAUNDERS, JW
影响因子：
3.4
作者：
SilosSantiago, I;Fagan, AM;Barbacid, M
通讯作者：
Barbacid, M
DOI：
10.1523/jneurosci.6412-11.2012
发表时间：
2012-04-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Sahara S;Yanagawa Y;O'Leary DD;Stevens CF
通讯作者：
Stevens CF
影响因子：
25
作者：
Wichterle, H;Garcia-Verdugo, JM;Alvarez-Buylla, A
通讯作者：
Alvarez-Buylla, A
影响因子：
2.6
作者：
Hadjantonakis, AK;Gertsenstein, M;Nagy, A
通讯作者：
Nagy, A