GPR161-GLI3 repressor signaling at cilia directs apical constriction and cell fate during cranial neural tube closure.

ABSTRACT: Failure to close the cranial neural tube, known as exencephaly/anencephaly, is a lethal congenital defect. However, the mechanisms driving patterning and reshaping of the broad cranial neural folds are poorly understood. Loss of the primary cilium-localized G protein-coupled receptor GPR161 causes ectopic, excessive hedgehog signaling in the mouse neural tube and fully penetrant exencephaly. GPR161 promotes GLI3 transcriptional repressor (GLI3R) formation while preventing GLI2 transcriptional activator formation. Here, we studied the mechanisms underlying cranial closure in mice using a Gpr161 mutant allelic series, epistasis between Gpr161 knockout and GLI effectors, and in toto imaging of cell behavior. A functional non-ciliary Gpr161 knock-in implicated GPR161 ciliary localization direc

SUBMITTER: Brooks ER 

PROVIDER: S-EPMC12752497 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature