As nFGFR1 has been designated as a central neuro-ontogenic factor19,20, we propose that the depletion of cortical nFGFR1 in schizophrenia organoids leads to dysregulation of the key neuro-ontogenic programs and, consequently, arrests cortical neuronal development. Indeed, the inhibition of FGFR1 signaling (the predominant FGFR expressed) with PD173074, depleted nFGFR1 in the CZ of control hESC organoids, and inhibited cortical development, similar to as observed in the schizophrenia organoids. The BrdU pulse-chase experiment showed that blocking FGFR1 reduced cortical migration of new born cells and their differentiation to neurons. Furthermore, PD173074 exposes the role of FGFR1 in the formation of doublecortin expressing neuroblasts and TBR1 expressing neuroblasts/pioneer neurons. It also demonstrated the importance of FGFR1 signaling in the development of calretinin interneurons.
