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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 immune privilege. In the mammalian brain, microglia and border associated macrophages (BAMs) provide immune surveillance and scavenge wastes, yet how evolution shaped immune-cell diversity and function is not understood. In zebrafish, a vascular-derived mural lymphatic endothelial cell (muLEC) lineage 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 in part via control of cadherin-6 (cdh6). muLECs are more transcriptionally similar to BAMs than to other mammalian meningeal cells and share several functions in tissue homeostasis. However, BAMs are absent from zebrafish and muLECs from mice and humans. Analysis of osr2, LEC and BAM markers in diverse vertebrate species reveals muLECs as an ancient 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 physiological importance of meningeal scavenger cells and the developmental plasticity of LECs in generating specialised cell types throughout evolution.

ORGANISM(S): Mus musculus Danio rerio

PROVIDER: GSE270486 | GEO | 2025/11/07

REPOSITORIES: GEO

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