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Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo.

Yamamoto M, Beppu H, Takaoka K, Meno C, Li E, Miyazono K, Hamada H - J. Cell Biol. (2009)

Bottom Line: A Smad2-activating factor such as Activin also contributes to DVE formation by generating a region of VE positive for the Smad2 signal and negative for Smad1 signal.DVE is thus formed at the distal end of the embryo, the only region of VE negative for the Smad1 signal and positive for Smad2 signal.An inverse relation between the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests an involvement of antagonism between Smad1- and Smad2-mediated signaling.

View Article: PubMed Central - PubMed

Affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan. myamamoto@fbs.osaka-u.ac.jp

ABSTRACT
The anterior-posterior axis of the mouse embryo is established by formation of distal visceral endoderm (DVE) and its subsequent migration. The precise mechanism of DVE formation has remained unknown, however. Here we show that bone morphogenetic protein (BMP) signaling plays dual roles in DVE formation. BMP signaling is required at an early stage for differentiation of the primitive endoderm into the embryonic visceral endoderm (VE), whereas it inhibits DVE formation, restricting it to the distal region, at a later stage. A Smad2-activating factor such as Activin also contributes to DVE formation by generating a region of VE positive for the Smad2 signal and negative for Smad1 signal. DVE is thus formed at the distal end of the embryo, the only region of VE negative for the Smad1 signal and positive for Smad2 signal. An inverse relation between the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests an involvement of antagonism between Smad1- and Smad2-mediated signaling.

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Expansion of the region positive for DVE markers and negative for p-Smad1 in Lefty1 mutant embryos. Wild-type (A and B) or Lefty1−/− (C and D) embryos at E5.5 were subjected to immunohistofluorescence staining with antibodies to p-Smad1 (pS1; A and C, green) or to p-Smad2 (pS2; B and D, green). Merged images with nuclear staining (Nuc; red) are also shown. Green color in merged images indicates increased level of p-Smad1 or p-Smad2 staining. Bracket in D indicates the region (the epiblast and VE in the distal region) with increased p-Smad2 staining. Wild-type (L1+/+) or Lefty1−/− (L1−/−) embryos at E5.5 were also examined for expression of Hex (E and F) and Cerl (G and H). Bars, 50 µm.
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fig4: Expansion of the region positive for DVE markers and negative for p-Smad1 in Lefty1 mutant embryos. Wild-type (A and B) or Lefty1−/− (C and D) embryos at E5.5 were subjected to immunohistofluorescence staining with antibodies to p-Smad1 (pS1; A and C, green) or to p-Smad2 (pS2; B and D, green). Merged images with nuclear staining (Nuc; red) are also shown. Green color in merged images indicates increased level of p-Smad1 or p-Smad2 staining. Bracket in D indicates the region (the epiblast and VE in the distal region) with increased p-Smad2 staining. Wild-type (L1+/+) or Lefty1−/− (L1−/−) embryos at E5.5 were also examined for expression of Hex (E and F) and Cerl (G and H). Bars, 50 µm.

Mentions: Staining for p-Smad1 was apparent throughout the primitive endoderm and VE until E5.2 (Fig. 2, A and B). At E5.5, however, p-Smad1 had disappeared from DVE while it was still apparent in the proximal portion of VE (Fig. 2 C and Fig. S3). In Lefty1−/− embryos (n = 5), the region of VE negative for p-Smad1 expanded (Fig. 4, A and C) along with the expansion of the region positive for DVE markers (Fig. 4, E–H). Thus, p-Smad1 is lost when and where DVE is formed.


Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo.

Yamamoto M, Beppu H, Takaoka K, Meno C, Li E, Miyazono K, Hamada H - J. Cell Biol. (2009)

Expansion of the region positive for DVE markers and negative for p-Smad1 in Lefty1 mutant embryos. Wild-type (A and B) or Lefty1−/− (C and D) embryos at E5.5 were subjected to immunohistofluorescence staining with antibodies to p-Smad1 (pS1; A and C, green) or to p-Smad2 (pS2; B and D, green). Merged images with nuclear staining (Nuc; red) are also shown. Green color in merged images indicates increased level of p-Smad1 or p-Smad2 staining. Bracket in D indicates the region (the epiblast and VE in the distal region) with increased p-Smad2 staining. Wild-type (L1+/+) or Lefty1−/− (L1−/−) embryos at E5.5 were also examined for expression of Hex (E and F) and Cerl (G and H). Bars, 50 µm.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC2654303&req=5

fig4: Expansion of the region positive for DVE markers and negative for p-Smad1 in Lefty1 mutant embryos. Wild-type (A and B) or Lefty1−/− (C and D) embryos at E5.5 were subjected to immunohistofluorescence staining with antibodies to p-Smad1 (pS1; A and C, green) or to p-Smad2 (pS2; B and D, green). Merged images with nuclear staining (Nuc; red) are also shown. Green color in merged images indicates increased level of p-Smad1 or p-Smad2 staining. Bracket in D indicates the region (the epiblast and VE in the distal region) with increased p-Smad2 staining. Wild-type (L1+/+) or Lefty1−/− (L1−/−) embryos at E5.5 were also examined for expression of Hex (E and F) and Cerl (G and H). Bars, 50 µm.
Mentions: Staining for p-Smad1 was apparent throughout the primitive endoderm and VE until E5.2 (Fig. 2, A and B). At E5.5, however, p-Smad1 had disappeared from DVE while it was still apparent in the proximal portion of VE (Fig. 2 C and Fig. S3). In Lefty1−/− embryos (n = 5), the region of VE negative for p-Smad1 expanded (Fig. 4, A and C) along with the expansion of the region positive for DVE markers (Fig. 4, E–H). Thus, p-Smad1 is lost when and where DVE is formed.

Bottom Line: A Smad2-activating factor such as Activin also contributes to DVE formation by generating a region of VE positive for the Smad2 signal and negative for Smad1 signal.DVE is thus formed at the distal end of the embryo, the only region of VE negative for the Smad1 signal and positive for Smad2 signal.An inverse relation between the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests an involvement of antagonism between Smad1- and Smad2-mediated signaling.

View Article: PubMed Central - PubMed

Affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan. myamamoto@fbs.osaka-u.ac.jp

ABSTRACT
The anterior-posterior axis of the mouse embryo is established by formation of distal visceral endoderm (DVE) and its subsequent migration. The precise mechanism of DVE formation has remained unknown, however. Here we show that bone morphogenetic protein (BMP) signaling plays dual roles in DVE formation. BMP signaling is required at an early stage for differentiation of the primitive endoderm into the embryonic visceral endoderm (VE), whereas it inhibits DVE formation, restricting it to the distal region, at a later stage. A Smad2-activating factor such as Activin also contributes to DVE formation by generating a region of VE positive for the Smad2 signal and negative for Smad1 signal. DVE is thus formed at the distal end of the embryo, the only region of VE negative for the Smad1 signal and positive for Smad2 signal. An inverse relation between the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests an involvement of antagonism between Smad1- and Smad2-mediated signaling.

Show MeSH