Extended Data Fig. 9: Developmental trajectories of visual cortex MGE GABA cell types.

(a-c) UMAPs for MGE cells colored by subclass (a), cluster (b) and synchronized age (c). (d) Transcriptomic trajectory tree for MGE clusters starting from the common MGE GABA RG antecedent, with corresponding MET types labeled. Nodes are clusters subdivided by synchronized age, and edges represent antecedent-descendant relationship between adjacent nodes, with thicker end at the antecedent node and thinner end at the descendant node. Nodes are grouped by subclass, and adult clusters are labeled. Each MET type is enclosed within a dashed outline among the MGE cell clusters. BC, basket cells. MC, Martinotti cells. (e) Clusters are grouped together based on similar trajectories. Within each cluster group, all cells along their trajectories, including all antecedent nodes, are shown and are colored by cluster membership. (f) Spatial distribution of MGE subclasses and clusters within each subclass in P56 MERFISH data, based on the ABC-WMB Atlas¹⁴. (g) Marker genes illustrating cell type diversification along trajectories. (h) Cluster composition of all MGE cells at each age. Specifically, Ascl1 and Tead2 are strongly enriched in progenitor stage, followed by activation of Lhx6, Nkx2-1 and Lhx8, which are key regulators of development of MGE-derived GABAergic neurons^54,97,98. Nkx2-1 and Lhx8 are transiently expressed, while Lhx6 persists to adulthood. We also observed expression of Nfib and Sp9 in early stages of MGE cells, which slowly decrease and maintain low level expression in some adult cell types. Nfib, Sp9 and Nkx2-1 are enriched in Pvalb chandelier and Lamp5 Lhx6 subclasses even in adulthood, while they are downregulated during development in most other MGE cell types. While Sst is expressed early in embryonic stages, Pvalb is not expressed until after eye opening. Within the Pvalb subclass, group 1 with clusters 736 and 754 and group 2 with cluster 741 both correspond to the Pvalb MET 3 type (in L5). Cluster 736 emerges from 754 at P19. Group 3 contains clusters 742 and 752, with 742 corresponding to Pvalb MET 4 (in L2/3), and 752 diverging from 742 at P17 and corresponding to Sst MET 2. Group 4 with clusters 743, 744 and 747 (split at P11) corresponds to Pvalb MET 2 (in L6). The Th⁺ Pvalb cluster 735 corresponds to Pvalb MET 1 (in L6). However, the developmental trajectory of cluster 735 (emerging at P1) appears highly ambiguous, with its closest antecedent being Sst cluster 758. Many Sst clusters emerge relatively late within each group, with late activation of key genes. For example, Crh is activated around P5 and Crhr2 around P10. Trajectory analysis suggests that Crhr2⁺ clusters 811, 814, 818, 819 and 820 diverge from Crh⁺ cluster 758 around P5, with further divergence occurring after P19. In group 1, 757, 758 and 761 split at P20, 811 and 814 split at P12, and 818, 819 and 820 split at P21. In group 2, 795 is born around P14, while 797 and 806 diverge from 803 around P17–19. In group 3, all 5 clusters diverge from 792 at P19–21. In group 5, 777 splits from 780 at P19.