title: Zfyve9a regulates the proliferation of hepatic cells during zebrafish embryogenesis.
abstract: Zfyve9 is a FYVE domain protein first identified as a binding partner for SMAD2/3. In vitro studies indicate that it can function either positively or negatively in the TGF-beta signaling pathway depending on the cell lines used. However, the in vivo function of this protein remains to be investigated. We first analyzed the tissue distribution of zebrafish zfyve9a by in situ hybridization. To investigate the in vivo function of this gene, we performed morpholino mediated loss-of-function assays. We analyzed the expression patterns of liver (cp and fabp10a), pancreas (trypsin and insulin) or gut (fabp2) specific markers to determine whether the formation of these organs is affected by zfyve9a knockdown. We determined the specification of hepatoblast in the zfyve9a morphants (prox1a) and investigated the proliferation and survival of hepatic cells in the morphants by P-H3 staining and TUNEL assay respectively. We report here that zfyve9a is enriched in the zebrafish embryonic liver and required for hepatogenesis. Morpholino mediated knockdown of zfyve9a inhibits the formation of liver by day 4 while the other endoderm-derived organs appear unaffected. We demonstrated that the specification of hepatoblasts is normal in the zfyve9a morphants; however, the proliferation rate of these cells is reduced. Thus, our results reveal the liver-specific function of zfyve9a during early embryogenesis and indicate that the zfyve9a mediated signal is essential for the proliferation of hepatic cells during the expansion of liver bud.
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Guangzhou, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Liu
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Shu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D003001:Cloning, Molecular; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis; D041981:Gastrointestinal Tract / Q000196:embryology; D055786:Gene Knockout Techniques; D022781:Hepatocytes / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis; D007328:Insulin / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000493:pharmacokinetics; D008099:Liver / Q000196:embryology*; D060172:Morpholinos; D010179:Pancreas / Q000196:embryology; D014357:Trypsin / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000493:pharmacokinetics; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: C497193:FABP2 protein, zebrafish; D050556:Fatty Acid-Binding Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D060172:Morpholinos; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins; C513422:fatty acid-binding protein 10, zebrafish; D000098551:Prospero-Related Homeobox 1 Protein; C000591255:zfyve9a protein, zebrafish; D014357:Trypsin