2. Academic Validation
  3. Ependymal Yes-Associated Protein Promotes the Neural Regeneration Through Enhancing the Ependymal Cell-Derived Perilesional Glial Borders in Mice After Spinal Cord Injury

Ependymal Yes-Associated Protein Promotes the Neural Regeneration Through Enhancing the Ependymal Cell-Derived Perilesional Glial Borders in Mice After Spinal Cord Injury

  • Acta Physiol (Oxf). 2026 Feb;242(2):e70147. doi: 10.1111/apha.70147.
Jiashu Lian 1 2,  Xiaowu Lin 1,  Jiali Shi 3,  Mengxian Jia 1,  Wenbin Zhang 1,  Xin Yan 1,  Sheng Lu 1,  Dewei Xie 4,  Jian Zhou 1,  Zhoule Zhu 1,  Ziwei Fan 1,  Yaozhi He 1,  Yumin Wu 1,  Jianhong Dong 3,  Wei Zhang 3,  Kelun Huang 1,  Minyu Zhu 1,  Ying Wang 5,  Zhihui Huang 3,  Honglin Teng 1 6 7
Affiliations

Affiliations

  • 1 Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2 Department of Ultrasound, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 3 School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China.
  • 4 Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 5 Clinical Research Center, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, Zhejiang, China.
  • 6 Zhejiang-US Joint Laboratory for Aging and Neurological Disease Research, Wenzhou, Zhejiang, China.
  • 7 Zhejiang Key Laboratory for Aging and Neurological Disease Research, Wenzhou, Zhejiang, China.
PMID: 41454669 DOI: 10.1111/apha.70147
Abstract

Objectives: Ependymal cell-derived perilesional glial borders may play a beneficial role in neural regeneration after spinal cord injury (SCI). Yes-associated protein (YAP), a key transcriptional cofactor, is involved in the control of body organ size by regulating cell differentiation, proliferation, growth, and apoptosis; however, it remains unclear whether the roles and underlying mechanisms of YAP signaling regulate the ependymal cell-derived perilesional glial borders after SCI.

Methods: We established a dorsal cord incision injury mouse model. The YAPf/f; FoxJ1-CreERT2 (YAPFoxJ1-ERT2-CKO) mice and YAPf/f; FoxJ1-CreERT2; Rosa26tdTomato mice were generated to examine the roles of ependymal YAP signaling in SCI. The RNA-seq, western blot, immunostaining, and cell-fate tracing tools were used to investigate the underlying mechanisms of YAP signaling in the regulation of ependymal cell-derived perilesional glial borders after SCI.

Results: YAP was activated in ependymal cells after SCI. Interestingly, YAP deletion in ependymal cells (YAPFoxJ1-ERT2-CKO mice) aggravated the neuronal loss and impaired the formation of perilesional glial borders and then inhibited the functional recovery after SCI. Furthermore, YAP deletion inhibited the proliferation and differentiation of ependymal cells to astrocytes and oligodendrocytes and reduced the secretion of Neurotrophic Factors after SCI. Mechanically, RNA-seq revealed that the expression of Colorectal Neoplasia Differentially Expressed (CRNDE) was downregulated in YAPFoxJ1-ERT2-CKO mice. Furthermore, we found downregulation of P300 and β-catenin and upregulation of GSK-3β in YAP-/- ependymal cells after SCI.

Conclusion: Ependymal YAP signaling promotes the formation of ependymal cell-derived perilesional glial borders in mice through the P300-CRNDE-Wnt/β-catenin pathway after SCI, which provides a novel target for SCI.

Keywords

CRNDE; SCI; YAP; differentiation; ependymal cells; proliferation.

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