Togaram1 is expressed in the neural tube and its absence causes neural tube closure defects.

ABSTRACT: Neural tube closure defect pathomechanisms in human embryonic development are poorly understood. Here we identified spina bifida patients expressing novel variants of the TOGARAM gene family. TOGARAM1 has been associated with the ciliopathy Joubert syndrome, but its connection to spina bifida and role in neural development is unknown. We show that Togaram1 is expressed in the neural tube and Togaram1 knockout mice have abnormal cilia, reduced sonic hedgehog (Shh) signaling, abnormal neural tube patterning, and display neural tube closure defects. Neural stem cells from Togaram1 knockout embryos showed reduced cilia and defects in Shh signaling. Overexpression in IMCD3 and HEK293 cells of TOGARAM1 carrying the variant found in the spina bifida patient resulted in cilia defect along with red

SUBMITTER: Wang Y 

PROVIDER: S-EPMC11541697 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature