Document Detail

SMAD1 signaling is critical for initial commitment of germ cell lineage from mouse epiblast.
MedLine Citation:
PMID:  12351174     Owner:  NLM     Status:  MEDLINE    
Commitment of the germ cell lineage during embryogenesis depends on zygotic gene expression in mammals, but little is known about the signaling molecules required for germ cell formation. Here we show that the intracellular signaling molecule SMAD1, acting downstream of bone morphogenetic protein (BMP) receptors, is required for the commitment of germ cell lineage from epiblast in early mouse embryos. Smad1 homozygous mutant embryos (Smad1-/-) were generated by in-frame insertion of lacZ gene into an exon of the Smad1 gene. Most of the Smad1-/- embryos contained no primordial germ cells (PGCs) and had short allantois, while histological analysis and in situ hybridization for the mesoderm marker genes revealed that early mesoderm induction was normal in those embryos. Smad1 expression was observed in epiblast and in visceral endoderm during gastrulation, while only a few alkaline phosphatase-positive PGCs at 7.5 and 8.5 days post coitum (E7.5 and E8.5) expressed Smad1. Phosphorylated SMAD proteins were localized in the proximal region of epiblast at E6.0-6.5, where the progenitors of PGCs and of allantois reside. Single-cell reverse transcription-polymerase chain reaction analysis revealed that the expression of Smad1, -5 and -8 were sporadic and mutually independent in proximal epiblast cells. We also found that BMP4-induced differentiation of PGCs from epiblast in vitro was fully dependent on the existence of phosphorylated SMAD1. These results indicate that SMAD1 signaling possesses a critical and non-redundant function in the initial commitment of the germ cell lineage.
Katsuhiko Hayashi; Takashi Kobayashi; Takashi Umino; Ryo Goitsuka; Yasuhisa Matsui; Daisuke Kitamura
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Mechanisms of development     Volume:  118     ISSN:  0925-4773     ISO Abbreviation:  Mech. Dev.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-27     Completed Date:  2003-05-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9101218     Medline TA:  Mech Dev     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  99-109     Citation Subset:  IM    
Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, Yamazaki 2669, Noda, Chiba 278-0022, Japan.
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MeSH Terms
Alkaline Phosphatase / metabolism
Cell Lineage
Central Nervous System / embryology
DNA-Binding Proteins / genetics*,  metabolism*
Dose-Response Relationship, Drug
Gene Expression Regulation, Developmental*
In Situ Hybridization
Lac Operon
Mesoderm / metabolism
Mice, Inbred C57BL
Mice, Inbred DBA
Models, Genetic
Mutagenesis, Site-Directed
Oligonucleotides, Antisense / pharmacology
Phosphoproteins / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction*
Smad Proteins
Smad1 Protein
Smad5 Protein
Time Factors
Tissue Distribution
Trans-Activators / genetics*,  metabolism*
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Oligonucleotides, Antisense; 0/Phosphoproteins; 0/Smad Proteins; 0/Smad1 Protein; 0/Smad1 protein, mouse; 0/Smad5 Protein; 0/Smad5 protein, mouse; 0/Trans-Activators; EC Phosphatase

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