Axons pull on the brain, but tension does not drive cortical folding.
Axons pull on the brain, but tension does not drive cortical folding.
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DOI：
10.1115/1.4001683
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发表时间：
2010-07
期刊：
影响因子：
--
通讯作者：
Taber LA
中科院分区：
文献类型：
--
作者：
Xu G;Knutsen AK;Dikranian K;Kroenke CD;Bayly PV;Taber LA
在人类大脑发育期间，大脑皮层经历大量折叠，导致其特征性的高度卷曲形式。折叠是必要的，以适应大脑皮层的扩张;异常的皮层折叠与各种神经系统疾病有关，包括精神分裂症，癫痫，自闭症和精神发育迟滞。虽然这个过程需要机械力，但驱动折叠的具体力产生机制仍不清楚。两个最广泛接受的假设是（1）折叠是由皮质的差异生长引起的，以及（2）折叠是由轴突中产生的机械张力引起的。然而，支持这两种理论的直接证据都缺乏。在这里，我们表明，轴突确实在相当大的紧张局势下，在发展中的雪貂大脑，但组织应力的模式是不一致的因果关系的作用轴突紧张。特别是，显微解剖分析表明，显着的张力存在沿着轴突在皮质下白色物质束，以及那些径向排列内发展回（向外折叠）。然而，与先前的推测相反，轴突张力并不直接穿过发育中的脑回，这表明轴突张力并不驱动折叠。另一方面，使用计算（有限元）模型，我们表明，差异皮质生长伴随着重塑的基板导致向外的褶皱和应力场，与我们的显微解剖实验是一致的，支持涉及差异生长的机制。局部扰动，如皮层生长启动的时间差异，可以确保一致的折叠模式。这项研究表明，结合实验和计算力学可以用来评估形态发生的竞争假说，并阐明皮质折叠的生物力学。
During human brain development, the cerebral cortex undergoes substantial folding, leading to its characteristic highly convoluted form. Folding is necessary to accommodate the expansion of the cerbral cortex; abnormal cortical folding is linked to various neurological disorders, including schizophrenia, epilepsy, autism and mental retardation. Although this process requires mechanical forces, the specific force-generating mechanisms that drive folding remain unclear. The two most widely accepted hypotheses are (1) folding is caused by differential growth of the cortex and (2) folding is caused by mechanical tension generated in axons. Direct evidence supporting either theory, however, is lacking. Here we show that axons are indeed under considerable tension in the developing ferret brain, but the patterns of tissue stress are not consistent with a causal role for axonal tension. In particular, microdissection assays reveal that significant tension exists along axons aligned circumferentially in subcortical white matter tracts, as well as those aligned radially inside developing gyri (outward folds). Contrary to previous speculation, however, axonal tension is not directed across developing gyri, suggesting that axon tension does not drive folding. On the other hand, using computational (finite element) models, we show that differential cortical growth accompanied by remodeling of the subplate leads to outward folds and stress fields that are consistent with our microdissection experiments, supporting a mechanism involving differential growth. Local perturbations, such as temporal differences in the initiation of cortical growth, can ensure consistent folding patterns. This study shows that a combination of experimental and computational mechanics can be used to evaluate competing hypotheses of morphogenesis, and illuminate the biomechanics of cortical folding.
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