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Chunk #45 — Results — Loss of nFGFR1 signaling affects developmental genome programing

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Cerebral organoids reveal early cortical maldevelopment in schizophrenia-computational anatomy and genomics, role of FGFR1.
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Gene ontology (GO) analysis revealed many developmental categories overrepresented by the genes that were differentially expressed in nondifferentiated NPCs and NCCs (Table 2). The overrepresented categories included development of the nervous system, of the brain and its parts, cell pluripotency, proliferation, neuronal differentiation, axonal guidance and growth, synapse formation, glial development, and neuronal apoptosis. The same categories, with the exception of glial development, were overrepresented by genes affected by FGFR1(SP-/NLS)(TK-) in NPCs and/or NCCs. Thus, nFGFR1 appears to specifically control neuronal NPC development. Overexpression of active nFGFR1(SP-/NLS), along with the cAMP/BDNF/GDNF stimulation, affected genes of brain development, cell proliferation, neurogenesis, neuronal differentiation, and apoptosis. Thus, both insufficient and excessive nFGFR1 signaling disrupt neuro-ontogenic gene programs.Table 2Gene ontology analysis shows genes regulated between NPCs vs. NCCs, and genes affected by dominant negative nuclear FGFR1(SP-/NLS)TK-) or constitutively active nuclear FGFR1(SP-/NLS) (RNAseq)NPC vs. NCCNPC vs. NPC+ FGFR1(SP-/NLS)(TK-)NCC+ vs. NCC+ FGFR1(SP-/NLS)(TK-)NCC vs. NCC+ FGFR1(SP-/NLS)Neural development Synapse development, assemblyYes Synaptic plasticity NS/CNS developmentYesYes Brain parts developmentYesYesYes Forebrain developmentYes Cell proliferation, mitotic cycleYesYesYes Cell migrationYesYes NeurogenesisYesYesYes Cell adhesionYes Extracellular matrix, proteasesYesYes Cell, neuronal differentiationYesYesYes Axon developmentYes