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Capicua (CIC), a member of the high mobility group–box (HMG-box) superfamily of transcriptional repressors, is frequently mutated in human oligodendrogliomas. However, its functions in brain development and tumorigenesis remain poorly understood. Here, we report that brain-specific deletion of Cic compromises developmental transition of neuroblasts to immature neurons in mouse hippocampus and compromises normal neuronal differentiation. Combined gene expression and ChIP-seq analyses identified VGF as an important CIC-repressed transcriptional surrogate involved in neuronal lineage regulation. Aberrant VGF expression promotes neural progenitor cell proliferation by suppressing their differentiation. Mechanistically, we demonstrated that CIC represses VGF expression by tethering SIN3-HDAC to form a transcriptional corepressor complex. Mass spectrometry analysis of CIC-interacting proteins …