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. Author manuscript; available in PMC: 2017 Jan 18.
Published in final edited form as: Nat Cell Biol. 2016 Jul 18;18(8):886–896. doi: 10.1038/ncb3389

Figure 7. Yap reprograms the relative isotopic enrichment of nutritional nitrogen into nucleotide biosynthesis in a Glul-dependent manner to support liver growth.

Figure 7

(a) Scheme describing the long-term 15N-Spirulina feeding studies in adult fish.

(b) Abundance of 15N-labelled nucleotide (Deoxyinosine, Deoxyadenosine and Deoxyguanosine) isotopologues (M+2 fraction) from hydrolyzed genomic DNA of dissected livers from WT and lf:Yap fish, as determined by LC-MS. n=5 WT and lf:Yap adult livers; see Supplementary Table 4. *p<0.05, **p<0.01, two-sided Student's t-test, values represent the mean±SEM.

(c) Glul activity in liver lysates extracted from WT and lf:Yap fish in the presence or absence of MSO. n=12, 12, 18 and 10 biologically independent WT, WT+MSO, lf:Yap and lf:Yap+MSO adult liver lysates respectively; see Supplementary Table 4. *p<0.001, two-sided Student's t-test, values represent the mean±SEM.

(d) Immunohistochemical analysis of PCNA staining in liver sections from WT and lf:Yap transgenic fish 24 hr after exposure to DMSO or MSO. Scale bar: 50μm.

(e) Quantification of hepatocyte proliferation (PCNA+ cells/field) in liver sections from WT and lf:Yap transgenic fish 24 hr after exposure to DMSO or MSO. n=51, 47, 48 and 63 independent WT, WT+MSO, lf:Yap and lf:Yap+MSO immunohistochemically (PCNA) stained fields of view respectively. Fields of view were derived from 4 zebrafish; see Supplementary Table 4. ****p<0.0001, two-sided Student's t-test, values represent the mean±SEM.

(f) Effect of MSO intervention on liver:body weight ratios in WT and lf:Yap adult fish. n=12, 12, 11 and 10 WT, WT+MSO, lf:Yap and lf:Yap+MSO adult zebrafish respectively; see Supplementary Table 4. *p<0.05, two-sided Student's t-test, values represent the mean±SEM.