A differential requirement for ciliary transition zone proteins in human and mouse neural progenitor fate specification.

ABSTRACT: Studying ciliary genes in the context of the human central nervous system is crucial for understanding the underlying causes of neurodevelopmental ciliopathies. Here, we use pluripotent stem cell-derived spinal organoids to reveal distinct functions of the ciliopathy gene RPGRIP1L in humans and mice, and uncover an unexplored role for cilia in human axial patterning. Previous research has emphasized Rpgrip1l critical functions in mouse brain and spinal cord development through the regulation of SHH/GLI pathway. Here, we show that RPGRIP1L is not required for SHH activation or motoneuron lineage commitment in human spinal progenitors and that this feature is shared by another ciliopathy gene, TMEM67. Furthermore, human RPGRIP1L-mutant motoneurons adopt hindbrain and cervical identities inst

SUBMITTER: Wiegering A 

PROVIDER: S-EPMC11972330 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature