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. 2022 May 17;39(7):110811. doi: 10.1016/j.celrep.2022.110811

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© 2022 The Authors

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PMC Copyright notice

Schematic summary of the changes in the activity and localization of SHH signaling components identified in INPP5E mutant cortical organoids

(A) In control organoids, SMO ciliary levels are low and the GLI3 repressor form (GLI3R) suppressing SHH signaling predominates.

(B) In INPP5E mutant organoids, the ciliary localization of several negative and positive regulators of SHH signaling is disturbed. SMO, GLI2, GPR161, and several IFT proteins accumulate in the cilium. GLI3R levels are reduced, and SHH target genes are activated.