Data associated with the publication: Syngap1 and the development of murine neocortical progenitor cells

SYNGAP1 is a major regulator of synaptic plasticity through its interaction with synaptic scaffold proteins and modulation of Ras and Rap GTPase signaling pathways. SYNGAP1 mutations in humans are often associated with intellectual disability, epilepsy, and autism spectrum disorder. Syngap1 heterozygous loss-of-function in mice results in impaired LTP, premature maturation of dendritic spines, learning disabilities and seizures, reflecting the phenotypes of the human SYNGAP1 syndrome. 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 Syngap1 does not influence the properties of neocortical progenitors and their cellular output in mice. Despite careful histological analysis of progenitor numbers, division mode, and neocortical thickness, using validated staining methods and EdU labeling with positive controls, we failed to replicate the main findings from human organoids. This discrepancy highlights potential species-specific or methodological differences and raises significant questions about the broader relevance of SYNGAP1’s role in neurogenesis. The absence of cortical progenitor deficits in Syngap1 haploinsufficient mice, which exhibit cognitive deficits and seizures, indicates that these phenotypes do not arise from differences in neurogenesis but are more likely due to SYNGAP1's prominent role in the regulation of synapse function. (2025-06)