Given the broad neuro-ontogenic functions of nFGFR1 in NPCs and NCCs, we next asked if the loss of nFGFR1 function could arrest the ongoing cortical development in control hESC organoids, similar to as observed in cortical cells of the schizophrenia organoids. We used PD173074, which specifically inhibits FGFRs (R1 > R2 > R3 > R4)56. Since fgfr1 was the highest expressed fgfr gene in NPCs and NCCs (Supplementary Table 2; 1.0FGFR1 > 0.16FGFR2 > 0.26FGFR3 > 0.008FGFR4), the effects of PD173074 would likely reflect the FGFR1 blockade. After the initial 8 days of cortical development, structurally stable hESC cerebral organoids were incubated with 100 nM PD173074 or in drug-free medium for an additional 10 days, during the ongoing CZ expansion.
