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Dev Genes Evol
2006 Oct 01;21610:607-22. doi: 10.1007/s00427-006-0081-8.
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Subtilisin-like proprotein convertase activity is necessary for left-right axis determination in Xenopus neurula embryos.
Toyoizumi R, Takeuchi S, Mogi K.
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Signaling by members of TGF-beta superfamily requires the activity of a family of site-specific endopeptidases, known as Subtilisin-like proprotein convertases (SPCs), which cleave these ligands into mature, active forms. To explore the role of SPCs in lateral plate mesoderm (LPM) differentiation in Xenopus, two SPC inhibitors, decanoyl-Arg-Val-Lys-Arg-chloromethylketone (Dec-RVKR-CMK) and hexa-arginine, were injected into the left and rightLPM of Xenopus neurulae. Left-side injection caused heart-specific left-right reversal, and this phenotype was rescued by co-injection of mature Nodal protein. In contrast, right-side injection caused left-right reversal of both the heart and gut. Tailbud embryos were less sensitive to SPC inhibitors than neurula embryos. Injection of inhibitors into either side of neurula embryos completely abolished expression of the left-LPM-specific genes, Xnr-1, antivin, and pitx2. SPC1 enzyme (Furin) was injected into the left or rightLPM of mid-neurula embryos to determine the effect of enhancing SPC activity. Left-side injection of SPC1 did not cause a significant left-right reversal of the internal organs. However, right-side injection of SPC1 strongly induced the expression of Xnr-1 and pitx2 in the rightLPM, and caused 100% left-right reversal of both the heart and gut. These results suggest that moderate level of SPC activity in the rightLPM of the neurulae is necessary for proper left-right specification. Taken together, SPC enzymatic activity must be present in both LPMs for expression of the left-handed genes and left-right axis determination of the heart and gut in Xenopus embryos.
Angliker,
The synthesis of inhibitors for processing proteinases and their action on the Kex2 proteinase of yeast.
1993, Pubmed
Angliker,
The synthesis of inhibitors for processing proteinases and their action on the Kex2 proteinase of yeast.
1993,
Pubmed Beck,
The role of BMP signaling in outgrowth and patterning of the Xenopus tail bud.
2001,
Pubmed
,
Xenbase Beck,
Extraembryonic proteases regulate Nodal signalling during gastrulation.
2002,
Pubmed Birsoy,
XPACE4 is a localized pro-protein convertase required for mesoderm induction and the cleavage of specific TGFbeta proteins in Xenopus development.
2005,
Pubmed
,
Xenbase Braks,
Structure and expression of Xenopus prohormone convertase PC2.
1992,
Pubmed
,
Xenbase Branford,
Regulation of gut and heart left-right asymmetry by context-dependent interactions between xenopus lefty and BMP4 signaling.
2000,
Pubmed
,
Xenbase Breckenridge,
A role for BMP signalling in heart looping morphogenesis in Xenopus.
2001,
Pubmed
,
Xenbase Brennan,
Nodal activity in the node governs left-right asymmetry.
2002,
Pubmed Cameron,
Polyarginines are potent furin inhibitors.
2000,
Pubmed Chang,
Smad5 is essential for left-right asymmetry in mice.
2000,
Pubmed Charng,
A constitutive mutation of ALK5 disrupts cardiac looping and morphogenesis in mice.
1998,
Pubmed
,
Xenbase Chen,
Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafish.
1997,
Pubmed Cheng,
The lefty-related factor Xatv acts as a feedback inhibitor of nodal signaling in mesoderm induction and L-R axis development in xenopus.
2000,
Pubmed
,
Xenbase Constam,
Tissue-specific requirements for the proprotein convertase furin/SPC1 during embryonic turning and heart looping.
2000,
Pubmed Constam,
Regulation of bone morphogenetic protein activity by pro domains and proprotein convertases.
1999,
Pubmed Constam,
SPC4/PACE4 regulates a TGFbeta signaling network during axis formation.
2000,
Pubmed Cui,
The activity and signaling range of mature BMP-4 is regulated by sequential cleavage at two sites within the prodomain of the precursor.
2001,
Pubmed
,
Xenbase Cui,
BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development.
1998,
Pubmed
,
Xenbase Degnin,
Cleavages within the prodomain direct intracellular trafficking and degradation of mature bone morphogenetic protein-4.
2004,
Pubmed
,
Xenbase Denault,
Furin/PACE/SPC1: a convertase involved in exocytic and endocytic processing of precursor proteins.
1996,
Pubmed Eimon,
Effects of heterodimerization and proteolytic processing on Derrière and Nodal activity: implications for mesoderm induction in Xenopus.
2002,
Pubmed
,
Xenbase Fugère,
Inhibitory potency and specificity of subtilase-like pro-protein convertase (SPC) prodomains.
2002,
Pubmed Fujiwara,
Distinct requirements for extra-embryonic and embryonic bone morphogenetic protein 4 in the formation of the node and primitive streak and coordination of left-right asymmetry in the mouse.
2002,
Pubmed Glavic,
Interplay between Notch signaling and the homeoprotein Xiro1 is required for neural crest induction in Xenopus embryos.
2004,
Pubmed
,
Xenbase Haramoto,
Xenopus tropicalis nodal-related gene 3 regulates BMP signaling: an essential role for the pro-region.
2004,
Pubmed
,
Xenbase Harland,
In situ hybridization: an improved whole-mount method for Xenopus embryos.
1991,
Pubmed
,
Xenbase Hartley,
Transgenic Xenopus embryos reveal that anterior neural development requires continued suppression of BMP signaling after gastrulation.
2001,
Pubmed
,
Xenbase Hashimoto-Partyka,
Nodal signaling in Xenopus gastrulae is cell-autonomous and patterned by beta-catenin.
2003,
Pubmed
,
Xenbase Hatsuzawa,
Purification and characterization of furin, a Kex2-like processing endoprotease, produced in Chinese hamster ovary cells.
1992,
Pubmed Hawley,
Disruption of BMP signals in embryonic Xenopus ectoderm leads to direct neural induction.
1995,
Pubmed
,
Xenbase Hyatt,
The left-right coordinator: the role of Vg1 in organizing left-right axis formation.
1998,
Pubmed
,
Xenbase Inman,
SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7.
2002,
Pubmed Isaac,
Control of vertebrate left-right asymmetry by a snail-related zinc finger gene.
1997,
Pubmed Jean,
alpha1-Antitrypsin Portland, a bioengineered serpin highly selective for furin: application as an antipathogenic agent.
1998,
Pubmed Kao,
The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos.
1988,
Pubmed
,
Xenbase Kidd,
Furin cleavage is not a requirement for Drosophila Notch function.
2002,
Pubmed Kishigami,
BMP signaling and early embryonic patterning.
2005,
Pubmed Kishigami,
BMP signaling through ACVRI is required for left-right patterning in the early mouse embryo.
2004,
Pubmed Korner,
Prohormone processing in Xenopus oocytes: characterization of cleavage signals and cleavage enzymes.
1991,
Pubmed
,
Xenbase Krebs,
Notch signaling regulates left-right asymmetry determination by inducing Nodal expression.
2003,
Pubmed Laping,
Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB-431542.
2002,
Pubmed Lowe,
Conserved left-right asymmetry of nodal expression and alterations in murine situs inversus.
1996,
Pubmed
,
Xenbase Lustig,
A Xenopus nodal-related gene that acts in synergy with noggin to induce complete secondary axis and notochord formation.
1996,
Pubmed
,
Xenbase Meno,
Diffusion of nodal signaling activity in the absence of the feedback inhibitor Lefty2.
2001,
Pubmed Meno,
Mouse Lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation.
1999,
Pubmed Mogi,
Xenopus neurula left-right asymmetry is respeficied by microinjecting TGF-beta5 protein.
2003,
Pubmed
,
Xenbase Nakayama,
Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins.
1997,
Pubmed Nelsen,
Proprotein convertase genes in Xenopus development.
2005,
Pubmed
,
Xenbase Onuma,
Multiple nodal-related genes act coordinately in Xenopus embryogenesis.
2002,
Pubmed
,
Xenbase Osada,
Xenopus nodal-related signaling is essential for mesendodermal patterning during early embryogenesis.
1999,
Pubmed
,
Xenbase Piedra,
BMP signaling positively regulates Nodal expression during left right specification in the chick embryo.
2002,
Pubmed Ramsdell,
Cardiac looping and the vertebrate left-right axis: antagonism of left-sided Vg1 activity by a right-sided ALK2-dependent BMP pathway.
1999,
Pubmed
,
Xenbase Rankin,
Regulation of left-right patterning in mice by growth/differentiation factor-1.
2000,
Pubmed Raya,
Notch activity induces Nodal expression and mediates the establishment of left-right asymmetry in vertebrate embryos.
2003,
Pubmed Raya,
Notch activity acts as a sensor for extracellular calcium during vertebrate left-right determination.
2004,
Pubmed Reissmann,
The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development.
2001,
Pubmed
,
Xenbase Reversade,
Depletion of Bmp2, Bmp4, Bmp7 and Spemann organizer signals induces massive brain formation in Xenopus embryos.
2005,
Pubmed
,
Xenbase Roebroek,
Failure of ventral closure and axial rotation in embryos lacking the proprotein convertase Furin.
1998,
Pubmed
,
Xenbase Saijoh,
Left-right patterning of the mouse lateral plate requires nodal produced in the node.
2003,
Pubmed Sampath,
Functional differences among Xenopus nodal-related genes in left-right axis determination.
1997,
Pubmed
,
Xenbase Sarac,
The furin inhibitor hexa-D-arginine blocks the activation of Pseudomonas aeruginosa exotoxin A in vivo.
2002,
Pubmed Schier,
Nodal signaling in vertebrate development.
2003,
Pubmed Schilling,
Regulation of left-right asymmetries in the zebrafish by Shh and BMP4.
1999,
Pubmed
,
Xenbase Schlange,
BMP2 is a positive regulator of Nodal signaling during left-right axis formation in the chicken embryo.
2002,
Pubmed Schneider,
The homeobox gene NKX3.2 is a target of left-right signalling and is expressed on opposite sides in chick and mouse embryos.
1999,
Pubmed Stieneke-Gröber,
Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease.
1992,
Pubmed Thomas,
Furin at the cutting edge: from protein traffic to embryogenesis and disease.
2002,
Pubmed Toyoizumi,
More than 95% reversal of left-right axis induced by right-sided hypodermic microinjection of activin into Xenopus neurula embryos.
2000,
Pubmed
,
Xenbase Toyoizumi,
Adrenergic neurotransmitters and calcium ionophore-induced situs inversus viscerum in Xenopus laevis embryos.
1997,
Pubmed
,
Xenbase Toyoizumi,
Xenopus nodal related-1 is indispensable only for left-right axis determination.
2005,
Pubmed
,
Xenbase Tsuji,
Secretory proprotein convertases PACE4 and PC6A are heparin-binding proteins which are localized in the extracellular matrix. Potential role of PACE4 in the activation of proproteins in the extracellular matrix.
2003,
Pubmed Tsuji,
Development of selectivity of alpha1-antitrypsin variant by mutagenesis in its reactive site loop against proprotein convertase. A crucial role of the P4 arginine in PACE4 inhibition.
2002,
Pubmed Ulloa,
Lefty proteins exhibit unique processing and activate the MAPK pathway.
2001,
Pubmed Wall,
Mesendoderm induction and reversal of left-right pattern by mouse Gdf1, a Vg1-related gene.
2000,
Pubmed
,
Xenbase Whitman,
Nodal signaling in early vertebrate embryos: themes and variations.
2001,
Pubmed
,
Xenbase Whitman,
TGF-beta superfamily signaling and left-right asymmetry.
2001,
Pubmed Xu,
Analysis of myostatin gene structure, expression and function in zebrafish.
2003,
Pubmed Yan,
Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation.
1999,
Pubmed Zakin,
Sirenomelia in Bmp7 and Tsg compound mutant mice: requirement for Bmp signaling in the development of ventral posterior mesoderm.
2005,
Pubmed
,
Xenbase Zhang,
Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node.
2001,
Pubmed
,
Xenbase
