Barão Soraia, Hong Ingie, Müller Ulrich, Huganir Richard L
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
bioRxiv. 2024 Dec 20:2024.12.18.629233. doi: 10.1101/2024.12.18.629233.
SYNGAP1 is a major regulator of synaptic plasticity through its interaction with synaptic scaffold proteins and modulation of Ras and Rap GTPase signaling pathways. mutations in humans are often associated with intellectual disability, epilepsy, and autism spectrum disorder. heterozygous loss-of-function results in impaired LTP, premature maturation of dendritic spines, learning disabilities and seizures in mice. More recently, SYNGAP1 was shown to influence cortical neurogenesis and the proliferation of progenitors in human organoids. Here, we show that the absence or haploinsufficiency of does not influence the properties of neocortical progenitors and their cellular output in mice. This discrepancy highlights potential species-specific or methodological differences and raises important questions about the broader applicability of SYNGAP1's role in neurogenesis.
SYNGAP1通过与突触支架蛋白相互作用以及调节Ras和Rap GTPase信号通路，成为突触可塑性的主要调节因子。人类中的突变通常与智力残疾、癫痫和自闭症谱系障碍相关。杂合性功能丧失会导致小鼠长时程增强受损、树突棘过早成熟、学习障碍和癫痫发作。最近，SYNGAP1被证明会影响人类类器官中皮质神经发生和祖细胞的增殖。在这里，我们表明SYNGAP1的缺失或单倍剂量不足不会影响小鼠新皮质祖细胞的特性及其细胞产出。这种差异突出了潜在的物种特异性或方法学差异，并引发了关于SYNGAP1在神经发生中的作用更广泛适用性的重要问题。
