{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nARHGAP11B is a human‐specific gene that arose through the partial duplication of ARHGAP11A and is preferentially expressed in neural progenitors during fetal neocortical development. Multiple studies have shown that its expression in radial glial cells potentiates basal progenitor amplification, leading to increased neuron production, cortical plate expansion, and even gyrification—a constellation of features that are thought to have driven the evolutionary expansion of the human neocortex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic investigations reveal that ARHGAP11B exerts its function, at least in part, via a mitochondria-based pathway. Once imported into mitochondria, ARHGAP11B interacts with the adenine nucleotide translocase and inhibits the mitochondrial permeability transition pore, thereby promoting glutaminolysis—a metabolic state that fuels the proliferation and self-renewal of basal progenitors. These actions have been corroborated in several experimental models, including developing ferret and marmoset neocortex, as well as in cerebral organoids, where modulation of ARHGAP11B levels is both necessary and sufficient to control basal progenitor abundance and neocortical size."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in neocortical expansion during evolution, sustained ARHGAP11B expression in transgenic mouse models results in enduring enhancement of neocortical size and improved cognitive behaviors, including increased memory flexibility and reduced anxiety in adulthood. Moreover, analyses in invasive ductal carcinoma of the breast have revealed that ARHGAP11B is aberrantly upregulated, suggesting that beyond its developmental functions, ARHGAP11B may play proto-oncogenic roles in tumor pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marta Florio, Mareike Albert, Elena Taverna, et al. 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