|ZFIN ID: ZDB-PUB-180122-2|
Chd7 Is Critical for Early T-Cell Development and Thymus Organogenesis in Zebrafish
Liu, Z.Z., Wang, Z.L., Choi, T.I., Huang, W.T., Wang, H.T., Han, Y.Y., Zhu, L.Y., Kim, H.T., Choi, J.H., Lee, J.S., Kim, H.G., Zhao, J., Chen, Y., Lu, Z., Tian, X.L., Pan, B.X., Li, B.M., Kim, C.H., Xu, H.
|Source:||The American journal of pathology 188(4): 1043-1058 (Journal)|
|Registered Authors:||Choi, Jung-Hwa, Kim, Cheol-Hee, Kim, Hyun-Taek|
|PubMed:||29353058 Full text @ Am. J. Pathol.|
Liu, Z.Z., Wang, Z.L., Choi, T.I., Huang, W.T., Wang, H.T., Han, Y.Y., Zhu, L.Y., Kim, H.T., Choi, J.H., Lee, J.S., Kim, H.G., Zhao, J., Chen, Y., Lu, Z., Tian, X.L., Pan, B.X., Li, B.M., Kim, C.H., Xu, H. (2018) Chd7 Is Critical for Early T-Cell Development and Thymus Organogenesis in Zebrafish. The American journal of pathology. 188(4):1043-1058.
ABSTRACTCHARGE syndrome is a congenital disorder affecting multiple organs and mainly caused by mutations in CHD7, a gene encoding a chromatin-remodeling protein. Immunodeficiency and reduced T-cells have been noted in CHARGE syndrome. However, the mechanisms underlying T-lymphopenia are largely unexplored. Here, we observed dramatic decrease of T cells in both chd7-knockdown and -knockout zebrafish embryos. Unexpectedly, hematopoietic stem and progenitor cells and, particularly, lymphoid progenitor cells were increased peripherally in nonthymic areas in chd7-deficient embryos, unlikely to contribute to the T cell decrease. Further analysis demonstrated that both the organogenesis and homing function of the thymus were seriously impaired. Chd7 might regulate thymus organogenesis through modulating the development of both neural crest cell-derived mesenchyme and pharyngeal endoderm-derived thymic epithelial cells. The expression of foxn1, a central regulator of thymic epithelium, was remarkably down-regulated in the pharyngeal region in chd7-deficient embryos. Moreover, the T-cell reduction in chd7-deficient embryos was partially rescued by overexpressing foxn1, suggesting that restoring thymic epithelium may be a potential therapeutic strategy for treating immunodeficiency in CHARGE syndrome. Collectively, the results indicated that chd7 was critical for thymic development and T-lymphopenia in CHARGE syndrome may be mainly attributed to the defects of thymic organogenesis. The current finding may benefit the diagnosis and therapy of T-lymphopenia and immunodeficiency in CHARGE syndrome.