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

Abstract

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.