Fig. 3

Mutations in the rpl6 gene result in compromised expansion of ptf1a-expressing pancreatic progenitor cells. (A) rpl6 expression is initially broad at 24 hpf, but high-level expression becomes increasingly restricted to the larval endoderm during the course of development. (B) Strong expression of rpl6 is observed in adult liver and pancreas. (C) An incross of rpl6^{hi3655b/ +} ;ptf1a:eGFP^jh1;ins:mCherry^jh2 adult fish results in 72 hpf embryos exhibiting reduced brain and eye size (green arrowhead), edema (red arrowhead), and poor yolk absorption (yellow arrowhead). Asterisks indicate grossly phenotypic rpl6hi3655b/hi3655b embryos. (D) Fraction of embryos from rpl6^{hi3655b/ +} ;ptf1a:eGFP^jh1;ins:mCherry^jh2 incross displaying gross developmental defects as assessed at 72 hpf (21% mutant, red; 79% wild type, blue) compared with control embryos generated by rpl6^{hi3655b/ +} ;ptf1a:eGFP^jh1;ins:mCherry^jh2 outcross (1.7% mutant, red; 98.3% wild type, blue). (E) The adult pancreas is grossly and histologically normal in rpl6^{hi3655b/ +} ;ptf1a:eGFP^jh1;ins:mCherry^jh2 heterozygotes. Note normal gross appearance of 7- month-old heterozygote, grossly normal pancreas including acinar cell mass (green), principal islet (yellow arrowhead), and secondary islets (white arrowheads), as well as normal adult histology. (F) ptf1a-expressing pancreatic progenitor cells fail to expand normally in embryos generated by rpl6^{hi3655b/ +} ;ptf1a:eGFP^jh1;ins:mCherry^jh2 incross. (G) Activation of trypsin expression occurs normally in rpl6hi3655b/hi3655b hypoplastic pancreas. (H) Incidence of abnormal pancreas development in embryos produced by either incross or outcross rpl6^{hi3655b/ +} ;ptf1a:eGFP^jh1; ins:mCherry^jh2 adults, expressed as the fraction of phenotypic (red) and wild-type (blue) embryos evaluated at 72 hpf. (I) Decreased incidence of persistent hypoplastic pancreas at 96 hpf indicates recovery of normal pancreatic mass in rpl6hi3655b/ + heterozygotes. A, adipose tissue. Color images available online at www.liebertpub.com/zeb