Figure 6: Model of cleavage angle regulation of cell fate during human cortical development.

(a) During early development, vRG divisions at the VZ are likely vertical, resulting in one daughter inheriting the basal fibre (BF), and both daughters inheriting half of the apical domain (AD) (orange). The daughter that retains the basal fibre maintains its apical contact and becomes a self-renewed vRG cell, whereas the daughter that does not receive the basal fibre likely also maintains its apical contact, generates a new basal fibre and adopts a vRG cell identity, thereby increasing the vRG progenitor population. (b) During peak neurogenesis, vRG divisions can either be vertical or horizontal/oblique. vRG division with vertical cleavage plane results in both daughter cells inheriting half of the AD. The cell that retains the basal fibre receives Notch and Integrin signalling via the basal fibre, maintains its apical contact and becomes a self-renewed vRG cell. The cell that does not inherit the basal fibre begins to express IP cell markers, including Notch ligands, thereby contributing to Notch activation of neighbouring vRG cells. The newly generated IP cell delaminates from the apical adhesion belt during the next cell cycle and migrates in a basal direction, where it may undergo multiple rounds of neurogenic divisions. (c) vRG division with a horizontal cleavage plane results in the more apical daughter inheriting the entire AD, regrowing a basal fibre, and becoming a self-renewed vRG cell. The more basal daughter inherits the basal fibre, rapidly exits the VZ and adopts an oRG cell fate. The newly generated oRG cell continues to divide horizontally, with the basal daughter inheriting the basal fibre and maintaining oRG cell identity. The apical daughter of horizontal oRG cell divisions either regrows a new fibre and adopts oRG cell fate, expanding the oRG cell population or becomes an IP cell and undergoes multiple rounds of neurogenic divisions.