PDF(Sci-hub)
Abstract：
Sociability entails some of the most complex behaviors processed by the central nervous system. It includes the detection, integration, and interpretation of social cues and elaboration of context-specific responses that are quintessentially species-specific. There is an ever-growing accumulation of molecular associations to autism spectrum disorders (ASD), from causative genes to endophenotypes across multiple functional layers; these however, have rarely been put in context with the opposite manifestation featured in hypersociability syndromes. Genetic copy number variations (CNVs) allow to investigate the relationships between gene dosage and its corresponding phenotypes. In particular, CNVs of the 7q11.23 locus, which manifest diametrically opposite social behaviors, offer a privileged window to look into the molecular substrates underlying the developmental trajectories of the social brain. As by definition sociability is studied in humans postnatally, the developmental fluctuations causing social impairments have thus far remained a black box. Here, we review key evidence of molecular players involved at both ends of the sociability spectrum, focusing on genetic and functional associations of neuroendocrine regulators and synaptic transmission pathways. We then proceed to propose the existence of a molecular axis centered around the paradigmatic dosage imbalances at the 7q11.23 locus, regulating networks responsible for the development of social behavior in humans and highlight the key role that neurodevelopmental models from reprogrammed pluripotent cells will play for its understanding.
摘要：
社交能力需要中枢神经系统处理的一些最复杂的行为。它包括检测，一体化,以及对社会线索的解释和对典型的物种特定的环境特定的反应的阐述。自闭症谱系障碍（ASD）的分子关联不断积累，从致病基因到跨多个功能层的内表型；然而，很少被放在具有超社交性综合症的相反表现的背景中。遗传拷贝数变异（CNV）允许研究基因剂量与其相应表型之间的关系。特别是,7q11.23基因座的CNVs，表现出截然相反的社会行为，提供了一个特权窗口来观察社会大脑发育轨迹的分子底物。根据定义，社交能力是在人类出生后研究的，迄今为止，导致社会损害的发展波动仍然是一个黑匣子。这里,我们回顾了社交光谱两端涉及分子参与者的关键证据，专注于神经内分泌调节因子和突触传递途径的遗传和功能关联。然后，我们继续提出以7q11.23基因座处的范式剂量失衡为中心的分子轴的存在，调节负责人类社会行为发展的网络，并强调来自重编程多能细胞的神经发育模型将对其理解发挥关键作用。
