Cerberus functions as a BMP agonist to synergistically induce <i>nodal</i> expression during left–right axis determination in the chick embryo

Yu, Xinmin; He, Fenglei; Zhang, Tao; Espinoza‐Lewis, Ramón A.; Lin, Liping; Yang, Jing

doi:10.1002/dvdy.21769

Cited by 10 publications

(8 citation statements)

References 54 publications

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“…In terms of Cerberus, the Xenopus isoform of the protein shows a strong phenotype towards BMP inhibition, as well as Wnt and Nodal antagonism . However, human and mouse Cerberus exhibit a significantly less pronounced phenotype towards BMP inhibition, despite showing strong in vitro binding to both BMP2 and BMP4 . In terms of SOST and USAG‐1, there is conflicting in vivo evidence to support SOST in the direct inhibition of BMP ligands, with more compelling evidence existing for USAG‐1 .…”

Section: Dan Family Of Bmp Antagonistsmentioning

confidence: 99%

The DAN family: Modulators of TGF‐β signaling and beyond

Nolan

Thompson

2014

Protein Science

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Extracellular binding proteins or antagonists are important factors that modulate ligands in the transforming growth factor (TGF-b) family. While the interplay between antagonists and ligands are essential for developmental and normal cellular processes, their imbalance can lead to the pathology of several disease states. In particular, recent studies have implicated members of the differential screening-selected gene in neuroblastoma (DAN) family in disease such as renal fibrosis, pulmonary arterial hypertension, and reactivation of metastatic cancer stem cells. DAN family members are known to inhibit the bone morphogenetic proteins (BMP) of the TGF-b family. However, unlike other TGF-b antagonist families, DAN family members have roles beyond ligand inhibition and can modulate Wnt and vascular endothelial growth factor (VEGF) signaling pathways. This review describes recent structural and functional advances that have expanded our understanding of DAN family proteins with regards to BMP inhibition and also highlights their emerging roles in the modulation of Wnt and VEGF signaling pathways.

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Section: Dan Family Of Bmp Antagonistsmentioning

confidence: 99%

The DAN family: Modulators of TGF‐β signaling and beyond

Nolan

Thompson

2014

Protein Science

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“…An interesting implication of this model is that one BMP-binding protein might simultaneously reduce receptor binding for high-affinity BMPs, reducing the problem of receptor saturation, while simultaneously increasing the receptor binding of low-affinity BMPs. The model might also apply to other BMP-binding molecules; for example, Cerberus, previously thought to be purely inhibitory, can also promote BMP signaling and also binds type I receptors (Yu et al, 2008). This will also result in an increase in the flow of the Cv2-binding proteins towards Cv2-expressing cells.…”

Section: Context-dependent Effects On Bmp Signal Reception: Crossveinmentioning

confidence: 99%

The extracellular regulation of bone morphogenetic protein signaling

2009

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In many cases, the level, positioning and timing of signaling through the bone morphogenetic protein (BMP) pathway are regulated by molecules that bind BMP ligands in the extracellular space. Whereas many BMP-binding proteins inhibit signaling by sequestering BMPs from their receptors, other BMP-binding proteins cause remarkably context-specific gains or losses in signaling. Here, we review recent findings and hypotheses on the complex mechanisms that lead to these effects, with data from developing systems, biochemical analyses and mathematical modeling.

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“…More recently in mouse kidney development, Cerberus has been shown to regulate the spatial organization within the ureteric tree, at least in part by antagonizing BMP-2 and -4 activity (Chi et al, 2011). In the chick embryo, Cerberus interacts with Nodal during left-right axis determination through complex interactions which appear to involve not only the induction of expression of Cerberus by Nodal on the left-side of the mesoderm (Tavares, Andrade, Silva, & Belo, 2007) but also the functioning of Cerberus in this process as a BMP coagonist rather than antagonist (Yu et al, 2008). Birds express Caronte, a close homologue of Cerberus which is also involved in left-right asymmetrical morphogenesis (Yokouchi, Vogan, Pearse, & Tabin, 1999).…”

Section: Cerberusmentioning

confidence: 98%