Although our classification system is limited compared to more recent molecular (notably ctip2 expression ref. 64) and functional approaches, (see refs 35, 36, 37 for reviews), our observations of increased spine density in TDP-43Q331K LVPNs compared to WT, when accounting for neuronal type (tufted and slender) ties into a broadening of ALS clinical features to include callosal and further cerebral involvement65, 66, 67 and is in line with widespread (regional and layer) cortical changes in rodent models21, 50. Here, BCL11B is linked to amyotrophic lateral sclerosis.