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Hereditas(Beijing) ›› 2022, Vol. 44 ›› Issue (9): 798-809.doi: 10.16288/j.yczz.22-193

• Research Article • Previous Articles     Next Articles

The role of the cd99l2 gene on leukocyte interstitial migration in zebrafish

Jing’ao Lu1,2(), Chunyan Huang1,2, Zhiyin Lin1,2, Zheng Tang1,2, Ning Ma1,2(), Zhibin Huang3()   

  1. 1. Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
    2. NMPA Key Laboratory for Safety Evaluation of Cosmetics, Southern Medical University, Guangzhou 510515, China
    3. Division of Development Biology & Regenerative Medicine, South China University of Technology, Guangzhou 510006, China;
  • Received:2022-06-13 Revised:2022-08-17 Online:2022-09-20 Published:2022-08-19
  • Contact: Ma Ning,Huang Zhibin E-mail:18609668060@163.com;mn1228@smu.edu.cn;huangzhb1986@scut.edu.cn
  • Supported by:
    Supported by the National Key Research and Development Program of China(2018YFA0801000);the National Natural Science Foundation of China No(31401231)

Abstract:

Leukocytes play an essential role in ontogeny, tissue regeneration, and innate and adaptive immunity. The migration of leukocytes to the infected or traumatized areas is necessary for their immune response function. As an adhesion molecule, CD99L2 is crucial in the extravasation of leukocytes, however, its role in the interstitial migration of leukocytes remains unclear. In this study, the cd99l2 gene was knock-out by TALEN (transcription activator-like effector nuclease) in zebrafish and discovered that the deletion had no effect on zebrafish development. The number of granulocytes and macrophages recruited to the wounded tissue was significantly reduced in the cd99l2 mutants following caudal fin damage. Further research revealed that the expression of mfap4 was drastically decreased in the cd99l2 mutants, which may be one of the reasons that affect the migration of macrophages to the wound site. Moreover,transgenic lines with labeled vasculature, neutrophils and macrophages demonstrated that neutrophils and macrophages migrate throughout the interstitial space to the wound tissue in both wild-type and mutant zebrafish at 60 hours post-fertilization, indicating that the cd99l2 gene is involved in the interstitial migration of leukocytes. Finally, RNA transcription, protein folding, and the P450 pathway were enriched in cd99l2 mutants by RNA-seq analysis. Previous research had demonstrated that the regulation of transcription and signal transduction could be affected by adhesion molecules, which may suggest that the cd99l2 gene is involved in the cascade signaling pathway of leukocyte migration as an adhesion molecule. In conclusion, this study uncovered a novel function of the cd99l2 gene in the process of leukocyte migration in zebrafish, which is expected to provide a theoretical foundation for inflammatory and immune-related diseases.

Key words: zebrafish cd99l2 gene, leukocyte migration, mfap4 gene, cascade signaling pathway