In vertebrates, hematopoietic stem cells (HSCs) are derived from hemogenic endothelium in the ventral wall of dorsal aorta via endothelial to hematopoietic transition (EHT), and then HSCs will migrate into zebrafish caudal hematopoietic tissue (CHT), which is the equivalent of fetal liver in human and mouse. However, little is known on molecular regulation of embryonic HSC maintenance.

Here, we isolate a zebrafish mutant with defective T lymphopoiesis using ENU mutagenesis. Positional cloning reveals that there is a T＞A point mutation in the second exon of Rpc9, a component of DNA-directed RNA polymerase III (Pol III) complex. Further analysis shows that rpc9 deficiency leads to the impairment of HSPCs survival in the CHT. Moreover, excessive apoptosis and the hematopoietic defects in rpc9−/− embryos can be fully rescued by downregulation of p53. Therefore, our work illustrates the tissue-specific role of Rpc9, a component of Pol III, in HSPC maintenance during zebrafish embryogenesis. This work has been published in Development and was supported by grants from the National Basic Research Program of China, the National Natural Science Foundation of China, and the Strategic Priority Research Program of the Chinese Academy of Sciences.

Website: http://dev.biologists.org/content/143/12/2103.long