Adducins regulate morphology and fate of neural progenitors during neocortical neurogenesis

The evolutionary expansion of the mammalian neocortex is driven by increased proliferative capacity of neural progenitor cells. However, the molecular machinery controlling the proliferation of apical and basal progenitors during neocortical development remains poorly understood. Here, we show that the three actin-associated morpho-regulatory adducins (ADD1-3) underlie the abundance of basal progenitors in the developing ferret and mouse neocortex in vivo and in human cortical organoids. Overexpression of adducins in the embryonic mouse neocortex enhances the number of basal progenitor protrusions, resulting in increased proliferative capacity and neuronal output. Conversely, knockout of ADD1 in human cortical organoids, which also leads to downregulation of other adducins, results in reduced progenitor abundance and aberrant neurogenesis. Hence, our findings establish adducins as critical regulators of neural progenitor proliferation and fate, key cellular features underlying the progression of mammalian neurogenesis.