1. Academic Validation
  2. Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish

Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish

  • iScience. 2021 Oct 30;24(11):103386. doi: 10.1016/j.isci.2021.103386.
Daoxi Lei 1 2 Xiuru Zhang 1 Muhammad Abdul Rouf 1 Yoga Mahendra 1 Lin Wen 1 Yan Li 1 Xiaojuan Zhang 1 Li Li 3 Luming Wang 1 Tao Zhang 1 Guixue Wang 1 Yeqi Wang 1
Affiliations

Affiliations

  • 1 Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China.
  • 2 Department of Ophthalmology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China.
  • 3 School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China.
Abstract

The differentiation of lymphatic progenitors is a crucial step in lymphangiogenesis. However, its underlying mechanism remains unclear. Here, we found that noncanonical Protease-activated Receptor 1 (par1) regulates the differentiation of lymphatic progenitors in zebrafish embryos. Loss of par1 function impaired lymphatic differentiation by downregulating prox1a expression in parachordal lymphangioblasts and caused compromised thoracic duct formation in zebrafish. Meanwhile, the G protein gnai2a, a par1 downstream effector, was selectively required for lymphatic development in zebrafish, and its mutation mimicked the lymphatic phenotype observed in par1 mutants. Interestingly, mmp13, but not Thrombin, was required for lymphatic development in zebrafish. Furthermore, analyses of genetic interactions confirmed that mmp13b serves as a par1 upstream Protease to regulate lymphatic development in zebrafish embryos. Mechanistically, par1 promotes flt4 expression and phospho-Erk1/2 activity in the posterior cardinal vein. Taken together, our findings highlight a function of par1 in the regulation of lymphatic differentiation in zebrafish embryos.

Keywords

Biological sciences; Immunology; Molecular biology.

Figures
Products