CLEAVAGE ORIENTATION AND THE ASYMMETRIC INHERITANCE OF NOTCH1 IMMUNOREACTIVITY IN MAMMALIAN NEUROGENESIS

Neurons in the mammalian central nervous system are generated from progenitor cells near the lumen of the neural tube. Time-lapse microscopy of dividing cells in slices of developing cerebral cortex reveals that cleavage orientation predicts the fates of daughter cells. Vertical cleavages produce behaviorally and morphologically identical daughters that resemble precursor cells; these symmetric divisions may serve to expand or maintain the progenitor pool. In contrast, horizontally dividing cells produce basal daughters that behave like young migratory neurons and apical daughters that remain within the proliferative zone. Notch1 immunoreactivity is distributed asymmetrically in mitotic cells, with Notch1 inherited selectively by the basal (neuronal) daughter of horizontal divisions. These results provide cellular and molecular evidence that cortical neurons are generated from asymmetric divisions.