Fig. 3: FOXG1-driven transcriptional programs direct the fate choice of LHX6^high CINs versus SINs/GP prototypic neurons in the MGE lineage.

a Heatmap of the top 500 most dynamic gene cascades for the MGE lineage trajectories in the control mice. Cells of each trajectory are ordered in columns based on their pseudotime. Color of top bars: cell identity. Color bar: smoothened spliced mRNA counts. b Scatterplots showing the expression levels of representative genes along the developmental trajectories for LHX6^high CINs, SINs, and GP prototypic neurons in the control mice. Dots: single cells. Vertical axis: normalized gene expression. Horizontal axis: cellular pseudotime of each trajectory. Color: cell identity. c Venn plot showing the number of overlapping genes among the top 500 pallial (LHX6^high CIN) most dynamic genes, the top 500 subpallial (SIN/GP prototypic neuron) most dynamic genes, and the MGE DEGs. Bar charts showing the identification of the three category DEGs of MGE. Highlighted genes are direct targets of FOXG1 (refer to Supplementary Data 4, 5). d Gene programs of connected modules identified by NMF. The connections among the 8 gene modules of different developmental stages in the MGE lineage and the top 10 ranked TFs of each gene module are shown. Dots: NMF modules; Connections indicate the transcription similarity between two modules; Genes among the MGE DEGs are bold (refer to Supplementary Data 3). e Immunostaining against mCherry and LHX6 at E16.5 in WT mice (E12.5 IUE) and quantification analysis of the percentage of pallial or subpallial mCherry⁺LHX6⁺ neurons among total mCherry⁺LHX6⁺ neurons distributed in the entire pallial and subpallial regions in two groups (n = 4 mice in pCAGIG-mCherry group, n = 5 mice in pCAGIG-mSox4-cDNA-mCherry group). Data are presented as means ± SEM. Two-tailed unpaired t test; ***P  <  0.001, ****P  <  0.0001; Pallium: ****P  <  0.0001, Subpallium: ***P  = 0.0001. Source data are provided as a Source Data file. White arrows: pallial mCherry⁺LHX6⁺ neurons, yellow arrows: subpallial mCherry⁺LHX6⁺ neurons. DEGs differential expression genes, NMF non-negative matrix factorization; TFs transcription factors, IUE in utero electroporation, WT wild type.