ZFIN Image: Nissim et al., 2016, Fig. 5

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Fig. 5

Nr5a2 chemical antagonist Cpd3 impacts exocrine pancreas development in vivo. (A) The Nr5a2 antagonist (Cpd3) produces reduced exocrine pancreas sizes that mimic the nr5a2^+/oz3 heterozygotes when treated from 12 to 72 hpf. (B) Quantification of exocrine pancreas size by area of trypsin expression at 72 hpf. Cpd3 significantly reduces exocrine pancreas size compared to vehicle (0.04% DMSO) treated controls (n=24 per group; p=0.007; unpaired t-test). (C) Loss of Nr5a2 activity by Cpd3 treatment does not visibly impact the formation of the insulin expressing β-cells. (D) Cpd3 treatment does not impact the size of the pdx1 pancreas progenitor pool at 48 hpf. (E) Quantification of pdx1 pancreas progenitor expression area at 48 hpf in control and Cpd3 treated groups (n>9 per group; p=0.9089; unpaired t-test). (F) Quantification of exocrine pancreas size by area of trypsin expression at 72 hpf. Heterozygote nr5a2^+/oz3 embryos show heightened sensitivity to 100 µM Cpd3 treatment relative to the nr5a2^+/+ sibling controls (n>10 per group; for control nr5a2^+/+vs. Cpd3 treated nr5a2^+/oz3, p<0.001; for control nr5a2^+/oz3vs. Cpd3 treated nr5a2^+/oz3, p=0.0004; for Cpd3 treated nr5a2^+/+vs. Cpd3 treated nr5a2^+/oz3, p=0.0042; ordinary one-way ANOVA with Tukey′s multiple comparisons test). (G) Drug treatment windows to examine the impact of Nr5a2 loss of function on distinct stages of pancreas and liver development, including progenitor specification, bud emergence, and organ differentiation and expansion. At 12 hpf, insulin expressing β-cells form within the gut tube (green dots). By 14 hpf, pdx1 expressing pancreas progenitors appear in two stripes (pink lines) An endocrine cell cluster (green) forms (beginning at approximately 24 hpf) and the dorsoventral pancreas bud emerges from the gut tube. By 40 hpf, the dorsoventral and anteroventral buds (blue arrows) have emerged from the gut tube, along with the liver bud (red arrow). Post 50 hpf, the liver and pancreas buds differentiate and expand. Figure adapted (Tiso et al., 2009).

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Acknowledgments

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Reprinted from Developmental Biology, 418(1), Nissim, S., Weeksb, O., Talbot, J.C., Hedgepeth, J.W., Wucherpfennig, J., Schatzman-Bone, S., Swinburne, I., Cortes, M., Alexa, K., Megason, S., North, T.E., Amacher, S.L., Goessling, W., Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development, 108-23, Copyright (2016) with permission from Elsevier. Full text @ Dev. Biol.