期刊
CEREBELLUM
卷 21, 期 5, 页码 801-813出版社
SPRINGER
DOI: 10.1007/s12311-022-01382-8
关键词
Primary cilia; Fragile X syndrome; FMRP; Cerebellum; Bergmann glia
资金
- National Institute of Mental Health [R01MH125979]
- National Institute on Aging [R21AG072423]
- UT Rising STARs award
- Simons Foundation Autism Research Initiative (SFARI) pilot award [574967]
The study revealed a reduction in the number of primary cilia and Sonic hedgehog (Shh) signaling in cerebellar Bergmann glia of Fmr1 KO mice, leading to reduced Granule Neuron Precursor (GNP) proliferation and thickness of the External Germinal Layer (EGL). This suggests that deficits in primary cilia of Bergmann glia may contribute to cerebellar developmental phenotypes in Fragile X Syndrome (FXS).
Primary cilia are non-motile cilia that function as antennae for cells to sense signals. Deficits of primary cilia cause ciliopathies, leading to the pathogenesis of various developmental disorders; however, the contribution of primary cilia to neurodevelopmental disorders is largely unknown. Fragile X syndrome (FXS) is a genetically inherited disorder and is the most common known cause of autism spectrum disorders. FXS is caused by the silencing of the fragile X mental retardation 1 (FMR1) gene, which encodes for the fragile X mental retardation protein (FMRP). Here, we discovered a reduction in the number of primary cilia and the Sonic hedgehog (Shh) signaling in cerebellar Bergmann glia of Fmr1 KO mice. We further found reduced granule neuron precursor (GNP) proliferation and thickness of the external germinal layer (EGL) in Fmr1 KO mice, implicating that primary ciliary deficits in Bergmann glia may contribute to cerebellar developmental phenotypes in FXS, as Shh signaling through primary cilia in Bergmann glia is known to mediate proper GNP proliferation in the EGL. Taken together, our study demonstrates that FMRP loss leads to primary ciliary deficits in cerebellar Bergmann glia which may contribute to cerebellar deficits in FXS.
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