We next inquired whether downregulation of nFGFR1 in differentiating cortical neurons (NCCs) and its robust expression in subcortical NPCs (Fig. 5, Supplementary Fig. 4; overexpression in schizophrenia iPSC-derived NPCs was shown in ref. 55) could affect neuro-ontogenic gene activities. Toward this goal, we analyzed the transcriptomes of homogenous 2D cultures of NPCs derived from H9 hESCs and of their NCC progeny. NCCs were induced by treatment (48 h) of NPCs with cAMP, BDNF, and GDNF29 (see Supplementary Materials and Methods). Loss of nFGFR1 function was instated by transfection of the dominant negative nFGFR1(SP-/NLS)(TK-). Twenty-four hours after transfection, cells were maintained in NPC medium or treated with the differentiating factors, AMP/BDNF/GDNF, for an additional 48 h. To model excessive nFGFR1 signaling, NPC cultures were transfected with constitutively active nFGFR1(SP-/NLS) and treated with AMP/BDNF/GDNF. Parallel controls were transfected with a β-galactosidase-expressing plasmid.
