Progranulin A-mediated MET signaling is essential for liver morphogenesis in zebrafish.
The mechanism that regulates embryonic liver morphogenesis remains elusive. Progranulin (PGRN) is postulated to play a critical role in regulating pathological liver growth. Nevertheless, the exact regulatory mechanism of PGRN in relation to its functional role in embryonic liver development remains to be elucidated. In our study, the knockdown of progranulin A (GrnA), an orthologue of mammalian PGRN, using antisense morpholinos resulted in impaired liver morphogenesis in zebrafish (Danio rerio). The vital role of GrnA in hepatic outgrowth and not in liver bud formation was further confirmed using whole-mount in situ hybridization markers. In addition, a GrnA deficiency was also found to be associated with the deregulation of MET-related genes in the neonatal liver using a microarray analysis. In contrast, the decrease in liver size that was observed in grnA morphants was avoided when ectopic MET expression was produced by co-injecting met mRNA and grnA morpholinos. This phenomenon suggests that GrnA might play a role in liver growth regulation via MET signaling. Furthermore, our study has shown that GrnA positively modulates hepatic MET expression both in vivo and in vitro. Therefore, our data have indicated that GrnA plays a vital role in embryonic liver morphogenesis in zebrafish. As a result, a novel link between PGRN and MET signaling is proposed.
Li
Yen-Hsing
YH
Molecular and Biological Agricultural Sciences Program, Taiwan International Graduate Program, National Chung Hsing University and Academia Sinica, Taipei 115, Taiwan.
Chen
Mark Hung-Chih
MH
Gong
Hong-Yi
HY
Hu
Shao-Yang
SY
Li
Ya-Wen
YW
Lin
Gen-Hwa
GH
Lin
Ching-Chun
CC
Liu
Wangta
W
Wu
Jen-Leih
JL
D000818:Animals; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000196:embryology*; D020320:Oligoribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D038081:Organogenesis / Q000187:drug effects / Q000502:physiology*; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000077153:Progranulins
D036341:Intercellular Signaling Peptides and Proteins; D020320:Oligoribonucleotides, Antisense; D019859:Proto-Oncogene Proteins c-met; D029961:Zebrafish Proteins; C509429:grna protein, zebrafish; D000077153:Progranulins