Figure 4.

Figure 4.

YTHDF2 acts as a bifurcation point leading to tissue-specific PCDs upon BHPF exposure. A, Survival analysis of embryos upon BHPF exposure with or without cotreatment with apoptosis and ferroptosis inhibitors; n = 45–50 per group. B, Effects of TNFα depletion (tnfα-MO) on BHPF-induced apoptosis (left panel), CVP defects (middle panel), and heart rate (right panel) in Tg(fli1a: eGFP) zebrafish embryos. C, Effects of cardiomyocyte-specific overexpression of gch1 on BHPF-induced heart rate reduction (Wild type zebrafish) and CVP defects (Tg(fli1a: eGFP) zebrafish). Red box indicates the heart region. The white dashed line indicates the trunk region. D, Schematic diagram of whole embryo, anterior, and tail parts for gene expression analysis (top panel). Expression levels of ptgs2a, sting1, and tnfα mRNA in whole embryo, fore, and tail trunks from untreated, BHPF exposed, ythdf2 knock-down (Morpholino) and ythdf2 mutant zebrafish embryos (bottom panel). E and F, Rescue effects of exogenous YTHDF2 and METTL3 on BHPF-mediated reduction of heart rate (E) and heart activity (F) as analyzed by DanioScope; n = 6–12 per group. G and H, Rescue effects of exogenous YTHDF2 and METTL3 on BHPF-mediated CVP apoptosis (G) and CVP defects (H); n = 9–17 per group (G). I, Schematic diagram illustrating the mechanism of YTHDF2-mediated tissue specific programmed cell deaths (PCDs) in embryos upon BHPF exposure. N denotes number of embryos for each experimental group. Quantification of the images on the left is shown in the right panels. Scale bar, 100 μm (B–C, G–H). BHPF treatment of zebrafish embryos from 4 hpf to the indicated time. Data are mean ± s.d. Student's t test, ns represents P > 0.05, ** represents P < 0.01, *** represents P < 0.001.