ZFIN ID: ZDB-PUB-110823-25
liver-enriched gene 1a and 1b Encode Novel Secretory Proteins Essential for Normal Liver Development in Zebrafish
Chang, C., Hu, M., Zhu, Z., Lo, L.J., Chen, J., and Peng, J.
Date: 2011
Source: PLoS One   6(8): e22910 (Journal)
Registered Authors: Hu, Minjie, Peng, Jinrong
Keywords: Embryos, Zebrafish, Liver development, Sequence alignment, Signal peptides, Liver, Morpholino, Protein secretion
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Western
  • Cell Cycle Checkpoints/genetics
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Gene Knockout Techniques
  • In Situ Hybridization
  • Larva/genetics
  • Larva/growth & development
  • Larva/metabolism
  • Liver/embryology
  • Liver/growth & development
  • Liver/metabolism*
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Phylogeny
  • Protein Isoforms/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Time Factors
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • Zebrafish Proteins/classification
  • Zebrafish Proteins/genetics*
PubMed: 21857963 Full text @ PLoS One

liver-enriched gene 1 (leg1) is a liver-enriched gene in zebrafish and encodes a novel protein. Our preliminary data suggested that Leg1 is probably involved in early liver development. However, no detailed characterization of Leg1 has been reported thus far. We undertook both bioinformatic and experimental approaches to study leg1 gene structure and its role in early liver development. We found that Leg1 identifies a new conserved protein superfamily featured by the presence of domain of unknown function 781 (DUF781). There are two copies of leg1 in zebrafish, namely leg1a and leg1b. Both leg1a and leg1b are expressed in the larvae and adult liver with leg1a being the predominant form. Knockdown of Leg1a or Leg1b by their respective morpholinos specifically targeting their 52-UTR each resulted in a small liver phenotype, demonstrating that both Leg1a and Leg1b are important for early liver development. Meanwhile, we found that injection of leg1-ATGMO, a morpholino which can simultaneously block the translation of Leg1a and Leg1b, caused not only a small liver phenotype but hypoplastic exocrine pancreas and intestinal tube as well. Further examination of leg1-ATGMO morphants with early endoderm markers and early hepatic markers revealed that although depletion of total Leg1 does not alter the hepatic and pancreatic fate of the endoderm cells, it leads to cell cycle arrest that results in growth retardation of liver, exocrine pancreas and intestine. Finally, we proved that Leg1 is a secretory protein. This intrigued us to propose that Leg1 might act as a novel secreted regulator that is essential for liver and other digestive organ development in zebrafish.