Loss of YY1 in Purkinje cells triggers cerebellar ataxia via Wnt10b-mediated impairment of dendrite development.
Overview
- School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China
- Centre for Cell and Developmental Biology, The Chinese University of Hong Kong, Hong Kong, China
- AoE Centre for Plant Vacuole Biology and Biotechnology, The Chinese University of Hong Kong, Hong Kong, China
- Gerald Choa Neuroscience Institute, The Chinese University of Hong Kong, Hong Kong, China
Abstract
The cerebellum relies on Purkinje cells (PCs) to coordinate motor functions and maintain neural circuitry. Impaired PC dendritogenesis is linked to neurological disorders, yet intrinsic molecular mechanisms remain unclear. We demonstrate that postnatal deletion of Yin Yang 1 (Yy1) in PCs disrupts dendrite and spine formation, impairs synaptic plasticity, and alters protein kinase C gamma (PKCγ) expression, leading to cerebellar ataxia and progressive atrophy. Mechanistically, YY1 transcriptionally activates wingless-type MMTV integration site family, member 10B (Wnt10b), which signals through Frizzled-4 (Fzd4) in PCs. Wnt10b downregulation mimics the dendritic defects seen in Yy1 mutants, indicating its crucial role in dendrite growth and synaptic environment regulation. These changes result in defective synapse innervation. Our findings reveal that YY1 governs PC dendritogenesis and synaptogenesis via Wnt10b, while also modulating PKCγ and β-catenin signaling. The YY1-Wnt10b axis emerges as a critical pathway underlying YY1-associated cerebellar dysfunction.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Code
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Data
Datasets cited
- geo:GSE336211, at NCBI GEO; found in “Data and code availability”
Data and code availability
RNA-seq data have been deposited at GEO and are publicly available as of the date of publication. Accession numbers are listed in the key resources table: GEO: GSE336211 (https://
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Versions
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Version 2, 28 September 2026
- Authors: added Kin Ming Kwan (0000-0002-1246-2398); removed Kin Ming Kwan
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 5 keywords, 2 funders, 64 references, 24 RRIDs.
Cite
This paper
Lui, Y. L., Dong, X., Leung, T. C. N., Li, T. H., Chan, T. F., & Kwan, K. M. (2026). Loss of YY1 in Purkinje cells triggers cerebellar ataxia via Wnt10b-mediated impairment of dendrite development. iScience, 29(8), 116975. https://
BibTeX
@article{lui2026loss,
author = {Lui, Ying Lam and Dong, Xiaonan and Leung, Thomas Chun Ning and Li, Tsz Ho and Chan, Ting Fung and Kwan, Kin Ming},
title = {{Loss of YY1 in Purkinje cells triggers cerebellar ataxia via Wnt10b-mediated impairment of dendrite development}},
journal = {iScience},
year = {2026},
month = jul,
volume = {29},
number = {8},
pages = {116975},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/
url = {https://
pmid = {42572605},
pmcid = {PMC13453040}
}
RIS
TY - JOUR
AU - Lui, Ying Lam
AU - Dong, Xiaonan
AU - Leung, Thomas Chun Ning
AU - Li, Tsz Ho
AU - Chan, Ting Fung
AU - Kwan, Kin Ming
TI - Loss of YY1 in Purkinje cells triggers cerebellar ataxia via Wnt10b-mediated impairment of dendrite development
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/
VL - 29
IS - 8
SP - 116975
SN - 2589-0042
PB - Elsevier
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
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