Extended Data Fig. 9: Summary of the effects of torsinA loss on NPC spatial organization and maturation.

a, Model of interphase NPC assembly in WT and torsinA-KO neurons. Onset of NPC assembly is not affected by torsinA deletion. Nuclear basket, inner ring, and transmembrane nucleoporins are recruited to the nascent NPC as the INM starts to bud. Instead of the normal INM-ONM fusion found in WT neurons, excessive INM extrusion causes NE blebs to emerge and enlarge in torsinA-KO neurons. These blebs stall torsinA-KO NPCs at an intermediate stage while NPC assembly completes in WT neurons. As torsinA-KO neurons continue to mature, NE blebs resolve and INM-ONM fusion occurs. Completion of NPC biogenesis is delayed in torsinA-KO neurons. b, Model of NPC localization in maturing WT (top) and torsinA-KO (bottom) neurons. In WT neurons, newly forming NPCs (blue) localize to empty spaces between existing NPCs (red), thereby maintaining uniform spatial organization. In maturing torsinA-KO neurons, newly forming NPCs (blue) localize abnormally close to each other or to existing NPCs (red), causing aberrant clusters. NPC biogenesis is upregulated in both genotypes and total NPC number is not affected by the absence of torsinA.