Document Detail


Porcupine homolog is required for canonical Wnt signaling and gastrulation in mouse embryos.
MedLine Citation:
PMID:  21554866     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Wnt signaling plays important roles in development and disease. The X-chromosomal Porcupine homolog gene (Porcn) encodes an evolutionary conserved member of the membrane bound O-acyl transferase (MBOAT) superfamily that has been shown to be required for the palmitoylation and secretion of Wnt3a, a mechanism that has been suggested to be conserved for all mammalian Wnt ligands. PORCN mutations in humans cause Focal Dermal Hypoplasia (FDH), a disorder causing developmental defects in heterozygous females and embryonic lethality in hemizygous males. In this study, Porcn mutant mouse embryonic stem (ES) cells were used to analyze the role of Porcn in mammalian embryonic development. In vitro, we show an exclusive requirement for Porcn in Wnt secreting cells and further, that any of the four Porcn isoforms is sufficient to allow for the secretion of functional Wnt3a. Embryos generated by aggregation of Porcn mutant ES cells with wildtype embryos fail to complete gastrulation in vivo, but remain in an epiblast-like state, similar to Wnt3 and Gpr177/Wls mutants. Consistent with this phenotype, in vitro differentiated mutant ES cells fail to generate endoderm and mesoderm derivatives. Taken together, these data confirm the importance of Porcn for Wnt secretion and gastrulation and suggest that disruption of early development underlies the male lethality of human PORCN mutants.
Authors:
Steffen Biechele; Brian J Cox; Janet Rossant
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-30
Journal Detail:
Title:  Developmental biology     Volume:  -     ISSN:  1095-564X     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-5-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Affiliation:
Department of Molecular Genetics, University of Toronto, ON, Canada M5S 1A8; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children Research Institute, Toronto, ON, Canada M5G 1X8.
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