XB-ART-8479Curr Opin Genet Dev 2001 Oct 01;115:533-40. doi: 10.1016/s0959-437x(00)00229-x.
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TGF-beta signalling pathways in early Xenopus development.
Many different ligands of the TGF-beta superfamily signal in the early Xenopus embryo and are required for the specification and patterning of the three germ layers as well as for gastrulation. Recent advances in the field are helping us understand how ligand activity is regulated both spatially and temporally, the mechanism by which the signals are transduced to the nucleus and how essentially the same signalling pathway can activate completely different sets of genes in different regions of the embryo.
PubMed ID: 11532395
Article link: Curr Opin Genet Dev
Species referenced: Xenopus
Genes referenced: bambi bmp2 bmp4 bmp7.1 bmpr1a cer1 chrd.1 ctnnb1 fgf4 foxh1 gdf1 mixer nodal1 nodal5.2 nodal6 smad1 smad2 smad3 smad4 smad6 smad6.2 smad7 smurf1 tgfb1 twsg1 uqcc6 vegt ventx2.2 zfyve9
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|Figure 1 TGF-β signalling pathways in early Xenopus development. The BMP pathway is shown on the left and the Activin-like signalling pathway is on the right. The BMP type II receptor is XBMPRII, and two BMP type I receptors are known, a Xenopus ALK3 (also called BR, for BMP receptor) and XALK2. The Activin type II receptor is XActRIIB and the type I receptor is XALK4. Multiple ligands are thought to interact with the receptor pairs. Receptor activation leads to phosphorylation and activation of R-Smads, which are XSmad1 and XSmad5 for the BMP receptors and XSmad2 and XSmad3 for the Activin receptors. XSmad2 and XSmad3 are thought to be recruited to the receptors by the membrane-associated protein, SARA. The R-Smads then form complexes with co-Smads, which are the constitutively nuclear XSmad4β at late blastula/early gastrula stages and XSmad4α at later stages, which is probably predominantly cytoplasmic in uninduced cells. Activated Smad complexes are recruited to DNA via specific transcription factors such as XOAZ for Smad1/Smad4 complexes and XFast-1 or Mixer for Smad2/Smad4 complexes. No recruiting transcription factors are yet known for Smad5/Smad4 or Smad3/Smad4 complexes. The pathway is further regulated at different points as shown. Ligand antagonists function extracellularly, probably preventing ligand binding to the receptor. The pseudoreceptor BAMBI is incorporated into receptor complexes but does not signal. Inhibitory Smads (XSmad6 and XSmad7) can act at the level of the receptors or in the case of Smad6, can also compete with Smad4 for activated Smad1. Smurf1 is an E3 ubiquitin ligase that targets Smad1 for degradation. (For details, see main text.)|
|Figure 2 Different transcription factor partners for activated XSmad2/XSmad4β complexes are expressed in different regions of the embryo. In situ hybridizations to visualize (a) XFast-1, (b) Mixer, or (c) XSmad2 mRNA (blue stain) in stage 10.25 Xenopus embryos that had been cut in half through the middle of the dorsal lip. Arrowhead, dorsal blastopore lip. XFast-1 mRNA is localized predominantly in the animal cap and in the prospective mesoderm throughout the marginal zone. Mixer, in contrast, is excluded from these regions and is expressed in a ring predominantly in prospective endoderm, and in involuting mesoderm. XSmad2 transcripts overlap with both the XFast-1 and Mixer transcripts.|