Convergent evolution of scavenger cell development at vertebrate brain borders

ABSTRACT: The vertebrate central nervous system (CNS) is protected by the blood brain barrier (BBB) and meningeal membranes, which ensure a state of immune privilege. In mammals, microglia and barrier associated macrophages (BAMs) provide immune surveillance and scavenge brain wastes, yet how evolution has shaped cell diversity and function in CNS immunity remains to be understood. Zebrafish meninges harbour a unique vascular-derived mural lymphatic endothelial cell (muLEC) type that fulfils scavenger cell functions at CNS borders. Here, we identify the transcription factor odd-skipped related 2 (osr2) as a specific marker and regulator of muLEC differentiation and maintenance. osr2 controls the transition of muLECs from interconnected endothelial cells to individual scavenger cells by suppressing downstream expression of cadherin 6 (cdh6). muLECs are more similar to BAMs than any other mammalian meningeal cell in the CNS and are activated to scavenge wastes upon injury. Nevertheless, BAMs are absent from zebrafish and muLECs from mice and humans. Evolutionary analysis of osr2, LEC and BAM marker gene expression in diverse species across taxa reveals muLECs as an ancient meningeal scavenger lineage and BAMs a recent mammalian specialisation. muLECs and BAMs share functional analogies but are not homologous, providing an example of convergent evolution. This highlights the functional importance of meningeal scavenger cells and the developmental plasticity of lymphatic endothelium in generating specialised cell types throughout evolution.

ORGANISM(S): Mus musculus Danio rerio

PROVIDER: GSE270486 | GEO | 2025/08/31

REPOSITORIES: GEO