Department of Basic Neurosciences, University of Geneva, CH-1202 Geneva, Switzerland.
INSERM U 1270, F-75005 Paris, France.
Science. 2021 Jan 22;371(6527). doi: 10.1126/science.aba4517.
The cerebral cortex is an intricate structure that controls human features such as language and cognition. Cortical functions rely on specialized neurons that emerge during development from complex molecular and cellular interactions. Neurodevelopmental disorders occur when one or several of these steps is incorrectly executed. Although a number of causal genes and disease phenotypes have been identified, the sequence of events linking molecular disruption to clinical expression mostly remains obscure. Here, focusing on human malformations of cortical development, we illustrate how complex interactions at the genetic, cellular, and circuit levels together contribute to diversity and variability in disease phenotypes. Using specific examples and an online resource, we propose that a multilevel assessment of disease processes is key to identifying points of vulnerability and developing new therapeutic strategies.
大脑皮层是一个复杂的结构，控制着人类的特征，如语言和认知。皮层功能依赖于在发育过程中从复杂的分子和细胞相互作用中出现的专门神经元。当这些步骤中的一个或几个执行不正确时，就会发生神经发育障碍。尽管已经确定了许多因果基因和疾病表型，但将分子破坏与临床表达联系起来的事件序列在很大程度上仍然不清楚。在这里，我们专注于人类皮质发育畸形，说明遗传、细胞和回路水平的复杂相互作用如何共同导致疾病表型的多样性和可变性。使用具体的例子和在线资源，我们提出对疾病过程进行多层次评估是识别脆弱点和开发新治疗策略的关键。
