Convergent evolution of scavenger cell development at brain borders

Gaudi, AU; Meier, M; Baltaci, OF; Chowdhary, S; Tulenko, FJ; Dudczig, S; Stamatis, SA; Paterson, S; Yu, H; Galeano, MCR; Mason, E; Miles, LB; Bryson-Richardson, RJ; Pask, AJ; Vukovic, J; Lagendijk, AK; Smith, KA; Kaslin, J; Harrison, MR; Currie, PD; Bower, NI; Hogan, BM

Author(s): Gaudi, AU; Meier, M; Baltaci, OF; Chowdhary, S; Tulenko, FJ; Dudczig, S; Stamatis, SA; Paterson, S; Yu, H; Galeano, MCR; Mason, E; Miles, LB; Bryson-Richardson, RJ; Pask, AJ; Vukovic, J; Lagendijk, AK; Smith, KA; Kaslin, J; Harrison, MR; Currie, PD; Bower, NI; Hogan, BM;
Details: Publication Year 2026-03,Volume 651,Issue #8106,Page 743-751
Journal Title: Nature
Publication Type: Research article
Abstract: The vertebrate central nervous system is protected by the blood-brain barrier and meningeal membranes, which ensure immune privilege(1). In the mammalian brain, microglia and barrier-associated or border-associated macrophages (BAMs) provide immune surveillance and scavenge wastes(2), 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 central nervous system borders(3-5). 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 by means of control of cadherin-6. 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, lymphatic endothelial cell (LEC) and BAM markers in diverse vertebrate species reveals muLECs as an ancient lineage and BAMs a recent mammalian specialization. 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 specialized cell types throughout evolution.
Publisher: Springer Nature
Keywords: Animals; *Zebrafish/genetics/embryology; Humans; Endothelial Cells/cytology/metabolism; Mice; *Brain/cytology/immunology; Cell Differentiation; Zebrafish Proteins/metabolism/genetics; *Biological Evolution; Cell Lineage; Microglia/cytology; Cadherins/metabolism; Transcription Factors/metabolism/genetics; Macrophages/cytology/metabolism; Female; Male; Blood-Brain Barrier/cytology
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1038/s41586-025-10003-3
Open Access at Publisher's Site: https://doi.org/10.1038/s41586-025-10003-3
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-01-29 05:40:52

Last Modified: 2026-04-02 06:01:39