Vertebrate <i>crossveinless 2</i> is secreted and acts as an extracellular modulator of the BMP signaling cascade

Kamimura, Mika; Matsumoto, Ken; Koshiba‐Takeuchi, Kazuko; Ogura, Toshihiko

doi:10.1002/dvdy.20069

Cited by 36 publications

(42 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the interdigital shaping of the hand appears normal in Cv2 -/-mice ( Fig. 1E and data not shown), although this region expresses both Cv2 and Bmp2/4 (Kamimura et al, 2004). These findings indicate that the requirement for Cv2 is stage-and tissuedependent in mouse embryogenesis.…”

Section: The Function Of Cv2 Is Not Essential For All Bmpdependent Emmentioning

confidence: 70%

“…The other theory is that Cv2 enhances Bmp signaling, as does its fly homologue. A report (Kamimura et al, 2004) has shown that transfection of a Cv2 plasmid enhances the cellular response to Bmp4, as measured by Smad phosphorylation. We have also observed that the addition of Cv2 protein (6 nM) enhances Bmp4 (25 nM)-induced cartilage differentiation in cultured E14.5 mouse embryonic fibroblasts (M.I.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis

et al. 2006

View full text Add to dashboard Cite

We here report essential roles of the Bmp-binding protein crossveinless 2(Cv2; Bmper) in mouse organogenesis. In the null Cv2 mutant mouse,gastrulation occurs normally, but a number of defects are found in Cv2-expressing tissues such as the skeleton. Cartilage differentiation by Bmp4 treatment is reduced in cultured Cv2-/- fibroblasts. Moreover, the defects in the vertebral column and eyes of the Cv2-/- mouse are substantially enhanced by deleting one copy of the Bmp4 gene, suggesting a pro-Bmp role of Cv2 in the development of these organs. In addition, the Cv2-/- mutant exhibits substantial defects in Bmp-dependent processes of internal organ formation, such as nephron generation in the kidney. This kidney hypoplasia is synergistically enhanced by the additional deletion of Kcp (Crim2) which encodes a pro-Bmp protein structurally related to Cv2. This study demonstrates essential pro-Bmp functions of Cv2 for locally restricted signal enhancement in multiple aspects of mammalian organogenesis.

show abstract

Section: The Function Of Cv2 Is Not Essential For All Bmpdependent Emmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis

et al. 2006

View full text Add to dashboard Cite

show abstract

“…and M.B.O., unpublished). Vertebrate homologs of Cv2 can bind Bmps, and act variously as agonists or antagonists of Bmp signaling in different assays (Kamimura et al, 2004;Coffinier et al, 2002;Binnerts et al, 2004). It is not clear by what mechanism Cv2 promotes Bmp signaling during PCV formation.…”

Section: Discussionmentioning

confidence: 99%

Matching catalytic activity to developmental function: Tolloid-related processes Sog in order to help specify the posterior crossvein in theDrosophilawing

et al. 2005

View full text Add to dashboard Cite

The Drosophila tolloid (tld) and tolloid related(tlr) gene products belong to a family of developmentally important proteases that includes Bone Morphogenetic Protein 1 (Bmp1). Tld is required early in Drosophila development for proper patterning of dorsal embryonic structures, whereas Tlr is required later during larval and pupal stages of development. The major function of Tld is to augment the activity of Decapentaplegic (Dpp) and Screw (Scw), two members of the Bmp subgroup of the Tgfβ superfamily, by cleaving the Bmp inhibitor Short gastrulation (Sog). In this study, we provide evidence that Tlr also contributes to Sog processing. Tlr cleaves Sog in vitro in a Bmp-dependent manner at the same three major sites as does Tld. However, Tlr shows different site selection preferences and cleaves Sog with slower kinetics. To test whether these differences are important in vivo, we investigated the role of Tlr and Tld during development of the posterior crossvein (PCV) in the pupal wing. We show that tlr mutants lack the PCV as a result of too little Bmp signaling. This is probably caused by excess Sog activity, as the phenotype can be suppressed by lowering Sog levels. However, Tld cannot substitute for Tlr in the PCV; in fact, misexpressed Tld can cause loss of the PCV. Reducing levels of Sog can also cause loss of the PCV, indicating that Sog has not only an inhibitory but also a positive effect on signaling in the PCV. We propose that the specific catalytic properties of Tlr and Tld have evolved to achieve the proper balance between the inhibitory and positive activities of Sog in the PCV and early embryo, respectively. We further suggest that, as in the embryo, the positive effect of Sog upon Bmp signaling probably stems from its role in a ligand transport process.

show abstract

“…We identified the secreted BMP-binding protein Cvl2 as playing a crucial role in locally enhancing BMP activity in the two distinct domains at the NPB. Cvl2 has been described as both an activator and inhibitor of BMP signalling (Conley et al, 2000;Moser et al, 2003;Binnerts et al, 2004;Kamimura et al, 2004;Ambrosio et al, 2008). Like many other proteins that interact with BMPs, such as the BMP antagonist Chordin, Cvl2 contains cysteine-rich domains (Conley et al, 2000).…”

Section: Cvl2 Locally Enhances Bmp Activity At the Npb And Is Requirementioning

confidence: 99%

A BMP regulatory network controls ectodermal cell fate decisions at the neural plate border

2013

View full text Add to dashboard Cite

SUMMARYDuring ectodermal patterning the neural crest and preplacodal ectoderm are specified in adjacent domains at the neural plate border. BMP signalling is required for specification of both tissues, but how it is spatially and temporally regulated to achieve this is not understood. Here, using a transgenic zebrafish BMP reporter line in conjunction with double-fluorescent in situ hybridisation, we show that, at the beginning of neurulation, the ventral-to-dorsal gradient of BMP activity evolves into two distinct domains at the neural plate border: one coinciding with the neural crest and the other abutting the epidermis. In between is a region devoid of BMP activity, which is specified as the preplacodal ectoderm. We identify the ligands required for these domains of BMP activity. We show that the BMP-interacting protein Crossveinless 2 is expressed in the BMP activity domains and is under the control of BMP signalling. We establish that Crossveinless 2 functions at this time in a positive-feedback loop to locally enhance BMP activity, and show that it is required for neural crest fate. We further demonstrate that the Distal-less transcription factors Dlx3b and Dlx4b, which are expressed in the preplacodal ectoderm, are required for the expression of a cell-autonomous BMP inhibitor, Bambi-b, which can explain the specific absence of BMP activity in the preplacodal ectoderm. Taken together, our data define a BMP regulatory network that controls cell fate decisions at the neural plate border.

show abstract

Vertebrate crossveinless 2 is secreted and acts as an extracellular modulator of the BMP signaling cascade

Cited by 36 publications

References 75 publications

Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis

Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis

Matching catalytic activity to developmental function: Tolloid-related processes Sog in order to help specify the posterior crossvein in theDrosophilawing

A BMP regulatory network controls ectodermal cell fate decisions at the neural plate border

Contact Info

Product

Resources

About