New reporter zebrafish line unveils heterogeneity among lymphatic endothelial cells during development

Dev Dyn. 2021 May;250(5):701-716. doi: 10.1002/dvdy.286. Epub 2021 Jan 19.

Abstract

Background: In zebrafish, lymphatic endothelial cells (LECs) originate from multiple/several distinct progenitor populations and generate organ-specific lymphatic vasculatures. Cell fate and tissue specificities were determined using a combination of genetically engineered transgenic lines in which the promoter of a LEC-specific gene drives expression of a fluorescent reporter protein.

Results: We established a novel zebrafish transgenic line expressing eGFP under the control of part of the zebrafish batf3 promoter (Basic Leucine Zipper ATF-Like Transcription Factor 3). Spatiotemporal examination of Tg(batf3MIN:eGFP) transgenic fish revealed a typical lymphatic expression pattern, which does not perfectly recapitulate the expression pattern of existing LEC transgenic lines. eGFP+ cells constitute a heterogeneous endothelial cell population, which expressed LEC and/or blood endothelial cells (BEC) markers in different tissues. In addition, we characterize the renal eGFP+ cell as a population of interest to study kidney diseases and regeneration.

Conclusion: Our Tg(batf3MIN:eGFP) reporter zebrafish line provides a useful system to study LEC populations, of which heterogeneity depends on origin of progenitors, tissue environment and physiological conditions. We further developed a novel fish-adapted tissue clearing method, which allows deep imaging and 3D-visualization of vascular and lymphatic networks in the whole organism.

Keywords: 3D imaging; infectiology; lymphatic network; tissue clearing; zebrafish phenotyping.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Endothelial Cells*
  • Genes, Reporter*
  • Lymphatic Vessels / cytology*
  • Zebrafish*