scholarly journals Activin/Nodal signalling before implantation: setting the stage for embryo patterning

2014 ◽  
Vol 369 (1657) ◽  
pp. 20130539 ◽  
Author(s):  
Costis Papanayotou ◽  
Jérôme Collignon
Keyword(s):  
Transforming Growth Factor Beta ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Embryonic Stem ◽  
Signalling Pathway ◽  
Loss Of Function ◽  
Embryo Patterning ◽  
Developmental Progression ◽  
Growth Factor Beta

Activins and Nodal are members of the transforming growth factor beta (TGF-β) family of growth factors. Their Smad2/3-dependent signalling pathway is well known for its implication in the patterning of the embryo after implantation. Although this pathway is active early on at preimplantation stages, embryonic phenotypes for loss-of-function mutations of prominent components of the pathway are not detected before implantation. It is only fairly recently that an understanding of the role of the Activin/Nodal signalling pathway at these stages has started to emerge, notably from studies detailing how it controls the expression of target genes in embryonic stem cells. We review here what is currently known of the TGF-β-related ligands that determine the activity of Activin/Nodal signalling at preimplantation stages, and recent advances in the elucidation of the Smad2/3-dependent mechanisms underlying developmental progression.

scholarly journals The Role of the TGF-β Coreceptor Endoglin in Cancer

2010 ◽  
Vol 10 ◽  
pp. 2367-2384 ◽  
Author(s):  
Eduardo Pérez-Gómez ◽  
Gaelle del Castillo ◽  
Juan Francisco Santibáñez ◽  
Jose Miguel Lêpez-Novoa ◽  
Carmelo Bernabéu ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tumor Development ◽  
Experimental Models ◽  
Type I ◽  
Type Ii ◽  
Invasion And Metastasis ◽  
Promising Target ◽  
Growth Factor Beta

Endoglin (CD105) is an auxiliary membrane receptor of transforming growth factor beta (TGF-β) that interacts with type I and type II TGF-β receptors and modulates TGF-β signaling. Endoglin is overexpressed in the tumor-associated vascular endothelium, where it modulates angiogenesis. This feature makes endoglin a promising target for antiangiogenic cancer therapy. In addition, recent studies on human and experimental models of carcinogenesis point to an important tumor cell–autonomous role of endoglin by regulating proliferation, migration, invasion, and metastasis. These studies suggest that endoglin behaves as a suppressor of malignancy in experimental and human epithelial carcinogenesis, although it can also promote metastasis in other types of cancer. In this review, we evaluate the implication of endoglin in tumor development underlying studies developed in our laboratories in recent years.

scholarly journals Suppression of canonical TGF-β signaling enables GATA4 to interact with H3K27me3 demethylase JMJD3 to promote cardiomyogenesis

2020 ◽  
Author(s):  
Andrew S. Riching ◽  
Etienne Danis ◽  
Yuanbiao Zhao ◽  
Yingqiong Cao ◽  
Congwu Chi ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Epigenetic Mechanism ◽  
Gene Promoters ◽  
Pathway Activation ◽  
Cardiac Gene ◽  
Growth Factor Beta ◽  
Heart Injury ◽  
Cardiac Transcription Factors

SummaryDirect reprogramming of fibroblasts into cardiomyocytes (CMs) represents a promising strategy to regenerate CMs lost after ischemic heart injury. Overexpression of GATA4, HAND2, MEF2C, TBX5, miR-1, and miR-133 (GHMT2m) along with transforming growth factor beta (TGF-β) inhibition efficiently promotes reprogramming. However, the mechanisms by which TGF-β blockade promotes cardiac reprogramming remain unknown. Here, we identify interactions between the histone H3 lysine 27 trimethylation (H3K27me3) – demethylase JMJD3, the SWI/SNF remodeling complex subunit BRG1, and cardiac transcription factors. Furthermore, canonical TGF-β signaling regulates the interaction between GATA4 and JMJD3. TGF-β activation impairs the ability of GATA4 to bind target genes and prevents demethylation of H3K27 at cardiac gene promoters during cardiac reprogramming. Finally, a mutation in GATA4 (V267M) exhibits reduced binding to JMJD3 and impaired cardiomyogenesis. Thus, we have identified an epigenetic mechanism wherein canonical TGF-β pathway activation impairs cardiac gene programming by interfering with GATA4-JMJD3 interactions.

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