13 Variant hepatocyte nuclear factor 1 and retinoic acid (RA) are reported to regulate liver specification as well.14, 15 RA regulation of wnt2bb is reported to be essential for liver specification in medaka as well.16 Shortly after the specification of hepatoblasts, hepatogenesis enters the “budding selleck inhibitor stage”: Hepatoblasts aggregate and form a thickened structure, termed liver bud. The intestinal primordium

undergoes a leftward bend (i.e., gut-looping) at approximately 30 hpf, which places the liver bud to the left side of the midline.17 The liver primordium continues to develop and enters the “expansion growth” stage at approximately 50 hpf: Hepatoblasts proliferate rapidly and undergo further morphogenesis selleck chemicals llc to reach the shape and place of the mature liver. It is in this period that hepatoblasts differentiate into mature hepatocytes as well as bile duct cells. Several recent studies have identified genes specifically required for the budding and growth of liver in the zebrafish. For example, mutation in def18 or myosin phosphatase target subunit 1 (mypt1)19 does not affect the specification of hepatoblasts, but inhibits the proliferation of these cells. The expansion growth of the liver requires genes, including liver-enriched gene

1 (leg1),20 npo,21 ubiquitin-like protein containing PHD and ring finger domains-1 (uhrf1),22 or DNA methyltransferase (dnmt)2.23 Embryos with mutation in translocase of outer mitochondrial membrane 22 (tomm22)24 or dnmt125 have normal early hepatogenesis, but show liver degeneration at later stages. Epigenetic-related genes, such as histone deacetylase (hdac)1/3, are involved in the regulation of liver development as well.26, 27 Although many critical regulators of hepatogenesis have been identified,

detailed understandings of liver development Dimethyl sulfoxide at the molecular and cellular levels remain to be established. Sorting nexin (SNX) family proteins are phox homology domain-containing proteins involved in diverse intracellular processes, such as endocytosis, protein sorting, and endosomal signaling.28, 29 The first SNX family member, SNX1, was discovered as an epidermal growth factor receptor (EGFR)-binding partner required for the lysosomal degradation of EGFR.30 Further studies demonstrated that SNX1, 2, 5, and 6 are components of the retromer that mediates the retrograde transport of transmembrane cargo from the endosome to the trans-Golgi network.31 SNX4 regulates the endosomal sorting of the transferrin receptor32 and SNX27 regulates the endosomal trafficking of G-protein–gated potassium channels, such as inwardly rectifying K, in neuronal cells.33 SNX17 enhances the endocytosis of the low-density lipoprotein (LDL) receptor as well as LDL-receptor–related protein.