ArticleGenes & development2005
Mice exclusively expressing the short isoform of Smad2 develop normally and are viable and fertile.
Article in Genes & development, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 108 citations in OpenAlex.
- SMAD2 linker phosphorylation impacts overall survival, proliferation, TGFβ1-dependent gene expression and pluripotency-related proteins in NSCLC.British journal of cancer · 2025Article
- The pivotal role of TGF-β/Smad pathway in fibrosis pathogenesis and treatment.Frontiers in oncology · 2025Review
- Therapeutic potential for renal fibrosis by targeting Smad3-dependent noncoding RNAs.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- A Nodal enhanced micropeptide NEMEP regulates glucose uptake during mesendoderm differentiation of embryonic stem cells.Nature communications · 2022Article
- Snrpb is required in murine neural crest cells for proper splicing and craniofacial morphogenesis.Disease models & mechanisms · 2022Article
- Structural basis for distinct roles of SMAD2 and SMAD3 in FOXH1 pioneer-directed TGF-β signaling.Genes & development · 2019Article
- Myofibroblast-Specific TGFβ Receptor II Signaling in the Fibrotic Response to Cardiac Myosin Binding Protein C-Induced Cardiomyopathy.Circulation research · 2018Article
- Systemic Activation of Activin A Signaling Causes Chronic Kidney Disease-Mineral Bone Disorder.International journal of molecular sciences · 2018Review
- Combinatorial Smad2/3 Activities Downstream of Nodal Signaling Maintain Embryonic/Extra-Embryonic Cell Identities during Lineage Priming.Cell reports · 2018Article
- Whole-transcriptome splicing profiling of E7.5 mouse primary germ layers reveals frequent alternative promoter usage during mouse early embryogenesis.Biology open · 2018Article
- The TGF-β Family in the Reproductive Tract.Cold Spring Harbor perspectives in biology · 2017Review
- Brd4-Brd2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification.EMBO reports · 2017Article
- Ribosomal Proteins Rpl22 and Rpl22l1 Control Morphogenesis by Regulating Pre-mRNA Splicing.Cell reports · 2017Article
- Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate.PLoS genetics · 2016Article
- Smad2 and Smad3 have differential sensitivity in relaying TGFβ signaling and inversely regulate early lineage specification.Scientific reports · 2016Article
- Article
- SMAD regulatory networks construct a balanced immune system.Immunology · 2013Review
- Function of alternative splicing.Gene · 2013Review
- Dihydroartemisinin ameliorates inflammatory disease by its reciprocal effects on Th and regulatory T cell function via modulating the mammalian target of rapamycin pathway.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Biological responses to TGF-β in the mammary epithelium show a complex dependency on Smad3 gene dosage with important implications for tumor progression.Molecular cancer research : MCR · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Smad2 and Smad3 are closely related effectors of TGFbeta/Nodal/Activin-related signaling. Smad3 mutant mice develop normally, whereas Smad2 plays an essential role in patterning the embryonic axis and specification of definitive endoderm. Alternative splicing of Smad2 exon 3 gives rise to two distinct protein isoforms. The short Smad2(Deltaexon3) isoform, unlike full-length Smad2, Smad2(FL), retains DNA-binding activity. Here, we show that Smad2(FL) and Smad2(Deltaexon3) are coexpressed throughout mouse development. Directed expression of either Smad2(Deltaexon3) or Smad3, but not Smad2(FL), restores the ability of Smad2-deficient embryonic stem (ES) cells to contribute descendants to the definitive endoderm in wild-type host embryos. Mice engineered to exclusively express Smad2(Deltaexon3) correctly specify the anterior-posterior axis and definitive endoderm, and are viable and fertile. Moreover, introducing a human Smad3 cDNA into the mouse Smad2 locus similarly rescues anterior-posterior patterning and definitive endoderm formation and results in adult viability. Collectively, these results demonstrate that the short Smad2(Deltaexon3) isoform or Smad3, but not full-length Smad2, activates all essential target genes downstream of TGFbeta-related ligands, including those regulated by Nodal.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.