Up-regulation of Minibrain/DYRK1A contributes to macrocephaly and brain overgrowth in a Drosophila model of fragile X syndrome - PubMed
3 days ago
- #Fragile X syndrome
- #DYRK1A
- #neurodevelopmental disorders
- Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability and autism, often associated with macrocephaly and brain overgrowth.
- The study reveals that Drosophila FMRP (dFmrp) suppresses the translation of Minibrain (Mnb)/DYRK1A, a kinase linked to Down syndrome and autism.
- Loss of dFmrp leads to Mnb up-regulation, causing macrocephaly and brain enlargement in Drosophila FXS models.
- Brain overgrowth starts early in development and can be mitigated with DYRK1A inhibitors.
- Mnb/DYRK1A signaling induces neuronal hypertrophy and excessive neural progenitor proliferation, driving brain enlargement.
- Mnb up-regulates protein synthesis; reducing Mnb activity or disrupting translational machinery restores brain size and improves locomotor coordination.
- The findings suggest shared molecular pathway disruptions in FXS, Down syndrome, and autism.