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- Syngap1 and the development of murine neocortical progenitor cellsPublication . Barao, Soraia; Xu, Yijun; Hong, Ingie; Müller, Ulrich; Huganir, Richard L.SYNGAP1 regulates synaptic plasticity through interactions with scaffold proteins and modulation of Ras and Rap GTPase signaling. Human SYNGAP1 mutations are linked to intellectual disability, epilepsy, and autism. In mice, Syngap1 haploinsufficiency causes impaired LTP, premature maturation of dendritic spines, learning disabilities, and seizures, reflecting the human phenotypes of SYNGAP1 syndrome. Recently, SYNGAP1 was shown to influence cortical neurogenesis and progenitor proliferation in human organoids. Here, we show that Syngap1 absence or haploinsufficiency does not alter neocortical progenitors and their cellular output in mice. Despite careful analysis of cortical progenitor properties, we fail to replicate the main findings from human organoids. This discrepancy suggests species-specific or methodological differences and raises questions about the broader relevance of SYNGAP1’s role in neurogenesis. The absence of cortical progenitor deficits in haploinsufficient mice, which exhibit cognitive deficits and seizures, indicates these arise from SYNGAP1’s regulation of synapse function rather than its role on neurogenesis.
- Basal progenitors as drivers of neocortical expansionPublication . Barao, Soraia; Müller, UlrichThe diversification and expansion of distinct progenitor cell subtypes during embryogenesis are essential to form the sophisticated brain structures present in vertebrates. In particular, the emergence of highly proliferative basal progenitors contributed to the evolutionary enlargement of the mammalian neocortex. Basal progenitors are at the center of indirect neurogenesis and can be divided into two main subtypes: the classical TBR2-positive intermediate progenitor cells and the outer radial glial cells, which are especially abundant in gyrencephalic species. While the function of some transcriptomic regulators is conserved across the mammalian clade, recent studies have identified human-specific genes and enhancers that uniquely affect progenitor biology, possibly driving the increased neocortical complexity and disease-susceptibility of the human brain. Here, we review the evolution of basal progenitors, highlighting species-specific traits, molecular drivers of proliferation, and how imbalances in neurogenesis contribute to human brain disorders.