Znhit3 regulates p53/p21 signaling and governs cerebellar granule cell development - PubMed
5 hours ago
- #p53/p21 signaling
- #Znhit3
- #cerebellar development
- Znhit3 mutations are linked to PEHO syndrome, characterized by cerebellar atrophy and intellectual disability.
- Conditional knockout of Znhit3 in mice leads to granule cell progenitor defects, including apoptosis, premature cell-cycle exit, and migration arrest.
- Znhit3 knockout results in cerebellar atrophy and motor deficits, with secondary effects on Purkinje cell alignment and synaptic organization.
- Transcriptomic analysis shows activation of the p53/p21 pathway and rRNA processing defects in Znhit3-knockout mice.
- Inhibition of p53/p21 signaling rescues granule cell progenitor development and cerebellar architecture in Znhit3-knockout mice.
- ZNHIT3 is identified as a critical regulator of ribosome biogenesis and cerebellar growth, suggesting therapeutic targets for related disorders.