FIGURE

Fig. S22

ID
ZDB-FIG-151009-45
Publication
Jia et al., 2015 - Mutation of kri1l causes definitive hematopoiesis failure via PERK-dependent excessive autophagy induction
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Fig. S22

S6K signaling is activated mainly in peripheral blood cells in kri1lcas002 mutants. (A) Representative immunoblotting analysis of Lc3, phospho-eif2a, phos-RPS6 and phos-S6K in whole embryos lysates of WT and kri1lcas002 embryos at 3 dpf with or without GSK2656157 treatment. (B) Working model for kri1l dysfunction-induced excessive autophagy in HSPCs and erythrocytes through different pathways. In kri1lcas002 mutants, ribosome biogenesis is abnormal due to inadequate 18S rRNA. It will lead to the accumulation of misfolded protein and subsequent PERK activation, which can trigger excessive autophagy and disrupt definitive hematopoiesis. Injection of perk MO, treatment with PERK inhibitor GSK2656157 or autophagy inhibitors can successfully restore defective hematopoiesis in kri1lcas002 mutants. (C-J) Representative confocal images of phos-RPS6 in the Tg(cmyb: egfp) transgenic background. Double staining of phos-RPS6 (red) and EGFP in the CHT region of embryos at 3 dpf. C and G show bright-field images overlaid with fluorescent staining. Scale bars, 50 µm. (K) The model of CHT region, in WT embryos, HSPCs localize in CHT region between arteries and venous for transitory expansion and differentiation, erythrocytes in the circulation present low level of phospho-RPS6. In mutants, HSPCs seed in CHT but take a poor proliferation, erythrocytes in circulation present higher phospho-RPS6 level, indicating the activation of S6K is dominant in peripheral blood cells.

Expression Data

Expression Detail
Antibody Labeling
Phenotype Data

Phenotype Detail
Acknowledgments
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