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 abundance of basal progenitors in the developing ferret and mouse neocortex in vivo and in human cortical organoids. Over expression of adducins in 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 down-regulation 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 progression of mammalian neurogenesis.