scholarly journals Protein Phosphatase 4 Cooperates with Smads to Promote BMP Signaling in Dorsoventral Patterning of Zebrafish Embryos

2012 ◽  
Vol 22 (5) ◽  
pp. 1065-1078 ◽  
Author(s):  
Shunji Jia ◽  
Fangyan Dai ◽  
Di Wu ◽  
Xia Lin ◽  
Cencan Xing ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Bmp Signaling ◽  
Zebrafish Embryos ◽  
Dorsoventral Patterning

Proteolytic cleavage of Chordin as a switch for the dual activities of Twisted gastrulation in BMP signaling

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4439-4447 ◽  
Author(s):  
Juan Larraín ◽  
Michael Oelgeschläger ◽  
Nan I. Ketpura ◽  
Bruno Reversade ◽  
Lise Zakin ◽  
...  
Keyword(s):  
Ternary Complex ◽  
Binding Assay ◽  
Bmp Signaling ◽  
Dominant Negative ◽  
Secreted Proteins ◽  
Dorsoventral Patterning ◽  
Twisted Gastrulation ◽  
Cognate Receptor ◽  
Licl Treatment ◽  
Bmp Antagonist

Dorsoventral patterning is regulated by a system of interacting secreted proteins involving BMP, Chordin, Xolloid and Twisted gastrulation (Tsg). We have analyzed the molecular mechanism by which Tsg regulates BMP signaling. Overexpression of Tsg mRNA in Xenopus embryos has ventralizing effects similar to Xolloid, a metalloprotease that cleaves Chordin. In embryos dorsalized by LiCl treatment, microinjection of Xolloid or Tsg mRNA restores the formation of trunk-tail structures, indicating an increase in BMP signaling. Microinjection of Tsg mRNA leads to the degradation of endogenous Chordin fragments generated by Xolloid. The ventralizing activities of Tsg require an endogenous Xolloid-like activity, as they can be blocked by a dominant-negative Xolloid mutant. A BMP-receptor binding assay revealed that Tsg has two distinct and sequential activities on BMP signaling. First, Tsg makes Chordin a better BMP antagonist by forming a ternary complex that prevents binding of BMP to its cognate receptor. Second, after cleavage of Chordin by Xolloid, Tsg competes the residual anti-BMP activity of Chordin fragments and facilitates their degradation. This molecular pathway, in which Xolloid switches the activity of Tsg from a BMP antagonist to a pro-BMP signal once all endogenous full-length Chordin is degraded, may help explain how sharp borders between embryonic territories are generated.

scholarly journals Diversification of metazoan Kexin-like proprotein convertases: insights from the leech Helobdella

2019 ◽  
Author(s):  
Wei-Yu Tao ◽  
Ya-Chih Cheng ◽  
Mi Hye Song ◽  
David A. Weisblat ◽  
Dian-Han Kuo
Keyword(s):  
Functional Divergence ◽  
Expression Patterns ◽  
Peptide Hormones ◽  
Cellular Communication ◽  
Bmp Signaling ◽  
Proteolytic Processing ◽  
Orthologous Group ◽  
Last Common Ancestor ◽  
Dorsoventral Patterning ◽  
Proprotein Convertases

AbstractIntercellular communication is quintessential for multicellularity and often mediated by secreted peptide ligands. In Metazoa, proprotein convertases are a major class of endoproteases partaking in the proteolytic processing of these ligands, which is in turn required for their signaling activities. In vertebrates, the best-studied convertase substrates are neuropeptides, peptide hormones, and members of the TGFβ/BMP-family. Each ligand is processed by a particular subset of convertases. Therefore, the diversification of convertases may have contributed to the growing complexity of cellular communication in metazoan evolution. However, proprotein convertases have not been systematically explored in Metazoa. Here, we sampled the representative metazoan genomes and established that six Kexin-like proprotein convertases were present in the last common ancestor of protostomes and deuterostomes. Among these, we identified a novel PCSKX orthologous group (OG) that was lost in vertebrates. Spiralian protosomes have, in general, maintained all six OGs. Therefore, we characterized the functional divergence of the Kexin-like OGs in the leech Helobdella, an experimentally tractable spiralian. Gene expression patterns suggested that PCSK1 and PCSK2 are specialized for the processing of neuropeptides and peptide hormones in bilaterians and that the newly identified PCSKX is probably functionally similar to furin and PCSK7. Finally, we showed that, distinct from the BMP morphogen in vertebrate embryos, the convertase-mediated proteolytic cleavage is not required for the short-range BMP signaling in the dorsoventral patterning of leech ectoderm. Together, our data revealed the complexity of the Kexin-like proprotein convertase gene family and their roles in generating diverse patterns of cellular communication in Metazoa.

scholarly journals Protein phosphatase magnesium-dependent 1A-mediated inhibition of BMP signaling is independent of Smad dephosphorylation

2010 ◽  
Vol 25 (8) ◽  
pp. 1895-1895
Author(s):  
Shoichiro Kokabu ◽  
Junya Nojima ◽  
Kazuhiro Kanomata ◽  
Satoshi Ohte ◽  
Tetsuya Yoda ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Bmp Signaling

scholarly journals Enhanced canonical Wnt signaling during early zebrafish development perturbs the interaction of cardiac mesoderm and pharyngeal endoderm and causes thyroid specification defects

2019 ◽  
Author(s):  
Isabelle Vandernoot ◽  
Benoît Haerlingen ◽  
Achim Trubiroha ◽  
Pierre Gillotay ◽  
Véronique Janssens ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Molecular Mechanisms ◽  
Cardiac Development ◽  
Wnt Signaling Pathway ◽  
Bmp Signaling ◽  
Thyroid Cell ◽  
Zebrafish Embryos ◽  
Cardiovascular Development ◽  
Fluorescent Reporter ◽  
Cardiac Mesoderm

AbstractBackgroundCongenital hypothyroidism (CH) due to thyroid dysgenesis is a frequent congenital endocrine disorder for which the molecular mechanisms remain unresolved in the far majority of cases. This situation reflects in part our still limited knowledge about the mechanisms involved in the early steps of thyroid specification from the endoderm, in particular the extrinsic signaling cues that regulate foregut endoderm patterning. In this study, we used small molecules and genetic zebrafish models to characterize the role of various signaling pathways in thyroid specification.MethodsWe treated zebrafish embryos during different developmental periods with small molecule compounds known to modulate the activity of Wnt signaling pathway and observed effects in thyroid, endoderm and cardiovascular development using whole mount in situ hybridization and transgenic fluorescent reporter models. We used an antisense morpholino to create a zebrafish acardiac model. For thyroid rescue experiments, BMP pathway induction in zebrafish embryos was obtained by using heatshock inducible transgenic lines.ResultsInterestingly, combined analyses of thyroid and cardiovascular development revealed that overactivation of Wnt signaling during early development leads to impaired thyroid specification concurrent with severe defects in the cardiac specification. When using a model of morpholino-induced blockage of cardiomyocyte differentiation, a similar correlation was observed, suggesting that defective signaling between cardiac mesoderm and endodermal thyroid precursors contributes to thyroid specification impairment. Rescue experiments through transient overactivation of BMP signaling could partially restore thyroid specification in models with defective cardiac development.ConclusionCollectively, our results indicate that BMP signaling is critically required for thyroid cell specification and identify cardiac mesoderm as a likely source of BMP signals.

A positive role for Short gastrulation in modulating BMP signaling during dorsoventral patterning in theDrosophilaembryo

Development ◽  
2001 ◽  
Vol 128 (19) ◽  
pp. 3831-3841 ◽  
Author(s):  
Eva Decotto ◽  
Edwin L. Ferguson
Keyword(s):  
Family Members ◽  
Positional Information ◽  
Dorsal Side ◽  
Bmp Signaling ◽  
Drosophila Embryo ◽  
Functional Difference ◽  
Ligand Specificity ◽  
Dorsoventral Patterning ◽  
Positive Role ◽  
Negative Function

Positional information in the dorsoventral axis of the Drosophila embryo is encoded by a BMP activity gradient formed by synergistic signaling between the BMP family members Decapentaplegic (DPP) and Screw (SCW). short gastrulation (sog), which is functionally homologous to Xenopus Chordin, is expressed in the ventrolateral regions of the embryo and has been shown to act as a local antagonist of BMP signaling. Here we demonstrate that SOG has a second function, which is to promote BMP signaling on the dorsal side of the embryo. We show that a weak, homozygous-viable sog mutant is enhanced to lethality by reduction in the activities of the Smad family members Mad or Medea, and that the lethality is caused by defects in the molecular specification and subsequent cellular differentiation of the dorsal-most cell type, the amnioserosa. While previous data had suggested that the negative function of SOG is directed against SCW, we present data that suggests that the positive activity of SOG is directed towards DPP. We demonstrate that Chordin shares the same apparent ligand specificity as does SOG, preferentially inhibiting SCW but not DPP activity. However, in Drosophila assays Chordin does not have the same capacity to elevate BMP signaling as does SOG, identifying a functional difference in the otherwise well conserved process of dorsoventral pattern formation in arthropods and chordates.

Protein phosphatase magnesium-dependent 1A inhibits BMP signaling by stimulating Smad degradation independent of dephosphorylation at the carboxyl termini

Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S26
Author(s):  
S. Kokabu ◽  
J. Nojima ◽  
T. Fukuda ◽  
K. Kanomata ◽  
T. Yoda ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Bmp Signaling

scholarly journals Protein phosphatase magnesium-dependent 1A–mediated inhibition of BMP signaling is independent of Smad dephosphorylation

2010 ◽  
Vol 25 (3) ◽  
pp. 653-660 ◽  
Author(s):  
Shoichiro Kokabu ◽  
Junya Nojima ◽  
Kazuhiro Kanomata ◽  
Satoshi Ohte ◽  
Tetsuya Yoda ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Bmp Signaling

scholarly journals BMP Signaling: Lighting up the Way for Embryonic Dorsoventral Patterning

2021 ◽  
Vol 9 ◽  
Author(s):  
Yifang Yan ◽  
Qiang Wang
Keyword(s):  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Bmp Signaling ◽  
Axis Formation ◽  
Dorsoventral Patterning ◽  
Significant Events ◽  
Similarities And Differences ◽  
Signaling Components ◽  
Molecular Nature

One of the most significant events during early embryonic development is the establishment of a basic embryonic body plan, which is defined by anteroposterior, dorsoventral (DV), and left-right axes. It is well-known that the morphogen gradient created by BMP signaling activity is crucial for DV axis patterning across a diverse set of vertebrates. The regulation of BMP signaling during DV patterning has been strongly conserved across evolution. This is a remarkable regulatory and evolutionary feat, as the BMP gradient has been maintained despite the tremendous variation in embryonic size and shape across species. Interestingly, the embryonic DV axis exhibits robust stability, even in face of variations in BMP signaling. Multiple lines of genetic, molecular, and embryological evidence have suggested that numerous BMP signaling components and their attendant regulators act in concert to shape the developing DV axis. In this review, we summarize the current knowledge of the function and regulation of BMP signaling in DV patterning. Throughout, we focus specifically on popular model animals, such as Xenopus and zebrafish, highlighting the similarities and differences of the regulatory networks between species. We also review recent advances regarding the molecular nature of DV patterning, including the initiation of the DV axis, the formation of the BMP gradient, and the regulatory molecular mechanisms behind BMP signaling during the establishment of the DV axis. Collectively, this review will help clarify our current understanding of the molecular nature of DV axis formation.

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