PUBLICATION

Sfrp5 Modulates Both Wnt and BMP Signaling and Regulates Gastrointestinal Organogensis in the Zebrafish, Danio rerio

Authors
Stuckenholz, C., Lu, L., Thakur, P.C., Choi, T.Y., Shin, D., and Bahary, N.
ID
ZDB-PUB-130605-16
Date
2013
Source
PLoS One   8(4): e62470 (Journal)
Registered Authors
Bahary, Nathan, Choi, Tae-Young, Shin, Donghun, Stuckenholz, Carsten, Thakur, Prakash Chandra
Keywords
none
MeSH Terms
  • Animals
  • Bone Morphogenetic Proteins/metabolism*
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Embryo, Nonmammalian/physiology
  • Endoderm/metabolism
  • Fertilization
  • Gastrointestinal Tract/embryology*
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Intercellular Signaling Peptides and Proteins/deficiency
  • Intercellular Signaling Peptides and Proteins/genetics
  • Intercellular Signaling Peptides and Proteins/metabolism*
  • Islets of Langerhans/embryology
  • Islets of Langerhans/metabolism
  • Liver/embryology
  • Liver/metabolism
  • Organ Size
  • Organogenesis*
  • Phenotype
  • Signal Transduction*
  • Tolloid-Like Metalloproteinases/antagonists & inhibitors
  • Wnt Proteins/metabolism*
  • Zebrafish/embryology*
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
23638093 Full text @ PLoS One
Abstract

Sfrp5 belongs to the family of secreted frizzled related proteins (Sfrp), secreted inhibitors of Wingless-MMTV Integration Site (Wnt) signaling, which play an important role in cancer and development. We selected sfrp5 because of its compelling expression profile in the developing endoderm in zebrafish, Danio rerio. In this study, overexpression of sfrp5 in embryos results in defects in both convergent extension (CE) by inhibition of non-canonical Wnt signaling and defects in dorsoventral patterning by inhibition of Tolloid-mediated proteolysis of the BMP inhibitor Chordin. From 25 hours post fertilization (hpf) to 3 days post fertilization (dpf), both overexpression and knockdown of Sfrp5 decrease the size of the endoderm, significantly reducing liver cell number. At 3 dpf, insulin-positive endodermal cells fail to coalesce into a single pancreatic islet. We show that Sfrp5 inhibits both canonical and non-canonical Wnt signaling during embryonic and endodermal development, resulting in endodermal abnormalities.

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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
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Engineered Foreign Genes
Mapping