Ward Claire, Sjulson Lucas, Batista-Brito Renata
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, United States.
Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY, United States.
Front Cell Neurosci. 2024 Sep 23;18:1465821. doi: 10.3389/fncel.2024.1465821. eCollection 2024.
Neurodevelopmental disorders (NDDs) are caused by abnormal brain development, leading to altered brain function and affecting cognition, learning, self-control, memory, and emotion. NDDs are often demarcated as discrete entities for diagnosis, but empirical evidence indicates that NDDs share a great deal of overlap, including genetics, core symptoms, and biomarkers. Many NDDs also share a primary sensitive period for disease, specifically the last trimester of pregnancy in humans, which corresponds to the neonatal period in mice. This period is notable for cortical circuit assembly, suggesting that deficits in the establishment of brain connectivity are likely a leading cause of brain dysfunction across different NDDs. Regulators of gene programs that underlie neurodevelopment represent a point of convergence for NDDs. Here, we review how the transcription factor MEF2C, a risk factor for various NDDs, impacts cortical development. Cortical activity requires a precise balance of various types of excitatory and inhibitory neuron types. We use MEF2C loss-of-function as a study case to illustrate how brain dysfunction and altered behavior may derive from the dysfunction of specific cortical circuits at specific developmental times.
神经发育障碍(NDDs)是由大脑发育异常引起的,导致脑功能改变,并影响认知、学习、自我控制、记忆和情感。NDDs在诊断时通常被划定为离散的实体,但实证证据表明,NDDs有大量重叠之处,包括遗传学、核心症状和生物标志物。许多NDDs在疾病的主要敏感期也有共性,特别是人类妊娠的最后三个月,这与小鼠的新生儿期相对应。这一时期以皮质回路组装为特征,表明大脑连接建立过程中的缺陷可能是不同NDDs脑功能障碍的主要原因。构成神经发育基础的基因程序调控因子是NDDs的一个汇聚点。在这里,我们综述了转录因子MEF2C(各种NDDs的一个风险因素)如何影响皮质发育。皮质活动需要各种兴奋性和抑制性神经元类型的精确平衡。我们以MEF2C功能丧失作为研究案例,来说明脑功能障碍和行为改变是如何在特定发育时期由特定皮质回路的功能障碍引起的。