Work

Pkd2l1 deletion inhibits the neurogenesis of cerebrospinal fluid-contacting neurons and impedes spinal cord injury repair

Year: 2025

Type: article

Abstract: Adult neural stem cells (NSCs) hold great promise for spinal cord injury (SCI) repair, but their identity in the mammalian spinal cord remains elusive. We previously demonstrated that Pkd2l1-positive cerebrospinal fluid-contacting neurons (CSF-cNs) harbor the NSC properties. Furthermore, elucidation of the molecular mechanism underlying the neurogenesis of CSF-cNs is crucial to SCI repair. Here, we utilized Pkd2l1−/− transgenic mice to investigate the role of Pkd2l1 in CSF-cN neurogenesis and SCI repair. We were shocked to find that the CSF-cN population was almost absent in Pkd2l1−/− mice. Following SCI, Pkd2l1−/− mice showed a significant reduction in NSCs surrounding the central canal. Notably, Pkd2l1−/− mice displayed deficient neuronal regeneration and impaired motor recovery after SCI. Collectively, our results demonstrate that Pkd2l1 plays a pivotal role in governing the neurogenesis of CSF-cN and the population of NSC, indicating its potential significance in advancing the development of more effective therapeutic approaches for SCI repair.

Source: Cell Death Discovery

DOI: 10.1038/s41420-025-02492-y