Time-Specific Effects of Spindle Positioning on Embryonic Progenitor Pool Composition and Adult Neural Stem Cell Seeding

The developmental mechanisms regulating the number of adult neural stem cells (aNSCs) are largely unknown. Here we show that the cleavage plane orientation in murine embryonic radial glia cells (RGCs) regulates the number of aNSCs in the lateral ganglionic eminence (LGE). Randomizing spindle orientation in RGCs by overexpression of Insc or a dominant-negative form of Lgn (dnLgn) reduces the frequency of self-renewing asymmetric divisions while favoring symmetric divisions generating two SNPs. Importantly, these changes during embryonic development result in reduced seeding of aNSCs. Interestingly, no effects on aNSC numbers were observed when Insc was overexpressed in postnatal RGCs or aNSCs. These data suggest a new mechanism for controlling aNSC numbers and show that the role of spindle orientation during brain development is highly time and region dependent. •Randomization of the spindle orientation changes the progenitor pool composition•Overexpression of Insc or dnLgn reduces asymmetric self-renewing division of aRGCs•The change in embryonic progenitor pool leads to reduced seeding of adult NSCs•Insc influences the seeding of adult NSCs in a narrow developmental time window Falk et al. uncover a new concept where the control of the division type in progenitor cells during embryonic development regulates the number of embryonic progenitor cells destined to become adult neural stem cells.