Physical biology of human brain development.
Physical biology of human brain development.
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DOI：
10.3389/fncel.2015.00257
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发表时间：
2015
影响因子：
5.3
通讯作者：
Kuhl E
中科院分区：
文献类型：
--
作者：
Budday S;Steinmann P;Kuhl E
神经发育是一个复杂的动态过程，涉及一系列精确协调的遗传、环境、生化和物理事件。发育生物学和遗传学塑造了我们对神经发育过程中分子和细胞机制的理解。最近的研究表明，物理力在将这些细胞机制转化为人脑复杂的表面形态方面发挥着核心作用。然而，神经元分化、迁移和连接对皮质折叠过程中物理力的精确影响仍然未知。在这里，我们从表面形态发生、模式选择和形状进化的角度回顾神经发育的细胞机制。我们重新审视皮质折叠作为多层系统中受限差异生长的不稳定性问题。为了确定差异生长的影响因素，我们绘制了人类神经发育的时间表，并强调了与极端径向和切向扩张相关的细胞事件。我们展示了差异生长的计算模型如何弥合从细胞水平的现象到器官水平的形式和功能的尺度，从而做出定量、个性化的预测。基于物理的模型可以量化皮质应力，识别关键折叠条件，合理化模式选择，并预测回旋波长和回旋指数。我们证明物理力量可以将皮质畸形解释为发育障碍的新兴特性。生物学和物理学的结合有望增进我们对人类大脑发育的理解，并实现皮质畸形的早期诊断，最终目标是改善癫痫、自闭症谱系障碍和精神分裂症等神经发育障碍的治疗。
Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales–from phenomena on the cellular level toward form and function on the organ level–to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.
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影响因子：
4.6
作者：
Budday S;Raybaud C;Kuhl E
通讯作者：
Kuhl E
影响因子：
12.7
作者：
Bradl M;Lassmann H
通讯作者：
Lassmann H
影响因子：
5.3
作者：
Budday S;Steinmann P;Kuhl E
通讯作者：
Kuhl E
影响因子：
3.6
作者：
Ballabh, P;Braun, A;Nedergaard, M
通讯作者：
Nedergaard, M
DOI：
10.1016/j.jmbbm.2015.02.024
发表时间：
2015-06
影响因子：
3.9
作者：
Budday, Silvia;Nay, Richard;de Rooij, Rijk;Steinmann, Paul;Wyrobek, Thomas;Ovaert, Timothy C.;Kuhl, Ellen
通讯作者：
Kuhl, Ellen