Meflin/ISLR is a meningeal cell-specific marker involved in the development of meninges and meningioma progression.

The meninges, which originate from the neural crest cells and mesoderm, play crucial roles in the formation, protection, and homeostasis of the central nervous system. Meningiomas, which arise from the meninges, are the most common primary intracranial tumors, and their recurrence and malignant transformation represent major clinical challenges. Recent studies have identified mesenchymal stromal cell- and fibroblast-expressing Linx paralogue (Meflin), as being expressed in the meninges, but its role in meningeal development and meningioma pathophysiology remains poorly understood. In this study, we investigated the expression patterns of Meflin during meningeal development and in meningioma tissues. Meflin expression was detected in the head of a Meflin reporter mouse line at approximately 11.5 days of embryonic life, suggesting its involvement in early meningeal development. Lineage-tracing experiments revealed that Meflin mRNA+ cells contribute to the postnatal formation and turnover of meningeal cells in adulthood, indicating their role in meningeal homeostasis. In human meningioma samples, Meflin expression was observed in normal meningeal cells and almost all tumor samples, with higher expression levels correlating with higher histological grades and increased recurrence rates. Analysis of a publicly available meningioma gene expression dataset revealed that tumors with high Meflin expression exhibited enhanced WNT ligand biogenesis and trafficking compared with tumors expressing low levels of Meflin. Furthermore, single-cell RNA sequencing analysis confirmed this finding and revealed elevated WNT6 expression specifically in clusters of Meflin-high tumor cells, highlighting a potential link between Meflin and WNT signaling activation in meningioma progression. Thus, this study provides novel insights into the role of Meflin in meningeal development and meningioma pathophysiology.