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The Primary Ciliary Deficits in Cerebellar Bergmann Glia of the Mouse Model of Fragile X Syndrome

Abstract

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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Data Availability

All data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Exing Wang for the technical support on imaging and Daisy Brockhouse for assisting with the analysis.

Funding

This work was supported by the National Institute of Mental Health (R01MH125979), the National Institute on Aging (R21AG072423), the UT Rising STARs award, and the Simons Foundation Autism Research Initiative (SFARI) pilot award (#574967).

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B.L. and L.B. conceived the study, performed the experiments, and wrote the manuscript. H.Y.L. supervised the whole project and wrote the manuscript.

Corresponding author

Correspondence to Hye Young Lee.

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Lee, B., Beuhler, L. & Lee, H.Y. The Primary Ciliary Deficits in Cerebellar Bergmann Glia of the Mouse Model of Fragile X Syndrome. Cerebellum (2022). https://doi.org/10.1007/s12311-022-01382-8

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  • DOI: https://doi.org/10.1007/s12311-022-01382-8

Keywords

  • Primary cilia
  • Fragile X syndrome
  • FMRP
  • Cerebellum
  • Bergmann glia