# Loss of meningeal lymphatic endothelial cells results in formation of a newly forming vascular network with scavenging function

**Authors:** Katharina Uphoff, Andreas van Impel, Lars Muhl, Martin Stehling, Christer Betsholtz, Stefan Schulte-Merker

PMC · DOI: 10.1242/dev.204988 · Development (Cambridge, England) · 2026-02-25

## TL;DR

Deleting specific brain lymphatic cells in zebrafish leads to a new vascular network that may help remove waste from the brain.

## Contribution

A new protocol for ablating brain lymphatic endothelial cells in zebrafish reveals compensatory vascular network formation.

## Key findings

- Ablated brain lymphatic endothelial cells do not regenerate in zebrafish.
- Loss of these cells disrupts meningeal blood vessels and arachnoid structure.
- A new vascular network forms with potential scavenging functions.

## Abstract

For an extended period of time, the meninges were believed to be devoid of lymphatic vessels. The recent discovery of lymphatic vessels in the dura mater of humans, mice and zebrafish, and the identification and characterization of scavenging lymphatic endothelial cells in zebrafish leptomeninges have contributed to a better understanding of waste removal routes from the brain. Zebrafish brain lymphatic endothelial cells (BLECs), in particular, have a high propensity for particulate waste removal from the cerebrospinal fluid. To further understand the function of BLECs, we have established a protocol for specifically ablating this cell type during embryonic stages. We show that BLECs do not recover upon complete depletion, even at adult stages. The absence of BLECs results in detrimental effects on the meningeal blood vasculature and on arachnoid mater structure. We further report that, upon BLEC ablation, a vessel network forms, which shares characteristics with lymphatic vessels and is able to take up substances injected into the brain parenchyma, thus possibly providing compensatory functions in the absence of BLECs.

Highlighted Article:
The ablation of scavenging lymphatic endothelial cells in the zebrafish leptomeninges disrupts meningeal blood vessels and results in the formation of an additional vascular network with scavenging capacity.

## Linked entities

- **Species:** Danio rerio (taxon 7955)

## Full-text entities

- **Genes:** eef1a1l1 (eukaryotic translation elongation factor 1 alpha 1, like 1) [NCBI Gene 30516] {aka EFL1-alpha, chunp6927, eef1a, ef1a, ik:tdsubc_2a3, ik:tdsubc_2b3}, her2 (hairy-related 2) [NCBI Gene 30300] {aka HER-2}, kdrl (kinase insert domain receptor like) [NCBI Gene 796537] {aka flk, flk-1, flk1, kdr, kdra, vegfr-2}, tjp1a (tight junction protein 1a) [NCBI Gene 378845] {aka cb817, tjp1, zo1.1}, itga9 (integrin, alpha 9) [NCBI Gene 394012] {aka zgc:63474}, prss1 (serine protease 1) [NCBI Gene 65223] {aka try, wu:fb57g08, zgc:109701}, lyve1b (lymphatic vessel endothelial hyaluronic receptor 1b) [NCBI Gene 564249] {aka fj84c10, lyve1, lyve1l, si:dkey-5a9.3, wu:fj84c10}, flt1 (fms related receptor tyrosine kinase 1) [NCBI Gene 544667] {aka VEGFR1, flt1b, sFlt1}, mrc1a (mannose receptor, C type 1a) [NCBI Gene 100286774] {aka im:5629217, mrc1}, flt4 (fms related receptor tyrosine kinase 4) [NCBI Gene 30121] {aka VEGFR3, cb1059}
- **Diseases:** inflammatory (MESH:D007249), lymphatic defects (MESH:D044148), vessel defects (MESH:C536223), cancer (MESH:D009369), T-DM1 (MESH:D009223), edema (MESH:D004487), brain edema (MESH:D001929), blood vessel defects (MESH:D009383), hemorrhage (MESH:D006470), stroke (MESH:D020521), neurological dysfunctions (MESH:D009461), infection (MESH:D007239), cytotoxic (MESH:D064420), breast cancer (MESH:D001943)
- **Chemicals:** nylon (MESH:D009757), methanol (MESH:D000432), NaCl (MESH:D012965), oxygen (MESH:D010100), thioether (MESH:D013440), EDTA (MESH:D004492), trastuzumab (MESH:D000068878), Triton X-100 (MESH:D017830), water (MESH:D014867), sodium azide (MESH:D019810), Kadcyla (MESH:D000080044), benzyl alcohol (MESH:D019905), 1-phenyl-2-thiourea (MESH:D010670), CaCl2 (MESH:D002122), Alexa-Fluor-647 cross (-), Alexa-647 (MESH:C569686), PMC (MESH:C008859), MgSO4 (MESH:D008278), MCC (MESH:C109691), PFA (MESH:C003043), agarose (MESH:D012685), lysine (MESH:D008239), KCl (MESH:D011189), benzyl benzoate (MESH:C006723), emtansine (MESH:D008453), DMSO (MESH:D004121), MS-222 (MESH:C003636)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Danio rerio (leopard danio, species) [taxon 7955], Homo sapiens (human, species) [taxon 9606], Gallus gallus (bantam, species) [taxon 9031]
- **Cell lines:** S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), BEC — Mus musculus (Mouse), Hybridoma (CVCL_RQ14), LEC — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_VU63)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12967140/full.md

## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC12967140/full.md

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Source: https://tomesphere.com/paper/PMC12967140