GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335515/primary200OKTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335515GEOGSEfalseNeurog1 and Neurog2 couple non-IT fate specification with cross-lineage cortical regionalization and bias recruitment into active circuitsThe neocortex comprises diverse neuronal subtypes with distinct projection patterns that emerge through sequential fate transitions. While combinatorial transcription factor (TF) activity is thought to drive this diversification, evidence from single-cell transcriptomics remains largely correlative. Here, by integrating single-cell transcriptomic data mining with double-knockout and split-Cre lineage-specific ablation in mice, we show that co-expression of the proneural TFs Neurog1 and Neurog2 is enriched in, and required to specify, non-intratelencephalic (non-IT) neuronal fates. Lineage tracing further reveals transient Neurog1/Neurog2 expression in intratelencephalic (IT) neurons, inhibitory interneurons, and astrocyte lineages, not specified by these TFs. Consistent with broader regulatory functions, integrative gene regulatory network analysis, single-cell meta-analysis, and spatial transcriptomics identify a Neurog1/Neurog2-co-regulated gene program delineating cortical regional identity. Additionally, lineage-labeled IT neurons show enrichment for immediate-early gene expression, with ~40% co-expressing Fos, suggesting activity-biased recruitment. Taken together, Neurog1/Neurog2 specify non-IT fates and engage gene programs shaping regional identity and circuit integration.2026/06/19GSE335515GSM981487034328335515Mus musculus