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Alexander F. Schier - One of the best experts on this subject based on the ideXlab platform.
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differential diffusivity of NODAL and lefty underlies a reaction diffusion patterning system
Science, 2012Co-Authors: Patrick Müller, Katherine W Rogers, Ben M Jordan, Joon S Lee, Drew N Robson, Sharad Ramanathan, Alexander F. SchierAbstract:Biological systems involving short-range activators and long-range inhibitors can generate complex patterns. Reaction-diffusion models postulate that differences in signaling range are caused by differential diffusivity of inhibitor and activator. Other models suggest that differential clearance underlies different signaling ranges. To test these models, we measured the biophysical properties of the NODAL/Lefty activator/inhibitor system during zebrafish embryogenesis. Analysis of NODAL and Lefty gradients revealed that NODALs have a shorter range than Lefty proteins. Pulse-labeling analysis indicated that NODALs and Leftys have similar clearance kinetics, whereas fluorescence recovery assays revealed that Leftys have a higher effective diffusion coefficient than NODALs. These results indicate that differential diffusivity is the major determinant of the differences in NODAL/Lefty range and provide biophysical support for reaction-diffusion models of activator/inhibitor-mediated patterning.
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NODAL stability determines signaling range
Current Biology, 2005Co-Authors: Ann Le J Good, Alexander F. Schier, Katherine Joubin, Antonio J Giraldez, Nadav Benhaim, Severine Beck, Yu Chen, Daniel B ConstamAbstract:Secreted TGFbeta proteins of the NODAL family pattern the vertebrate body axes and induce mesoderm and endoderm . NODAL proteins can act as morphogens , but the mechanisms regulating their activity and signaling range are poorly understood. In particular, it has been unclear how inefficient processing or rapid turnover of the NODAL protein influences autocrine and paracrine signaling properties . Here, we evaluate the role of NODAL processing and stability in tissue culture and zebrafish embryos. Removal of the pro domain potentiates autocrine signaling but reduces NODAL stability and signaling range. Insertion of an N-glycosylation site present in several related TGFbeta proteins increases the stability of mature NODAL. The stabilized form of NODAL acts at a longer range than the wild-type form. These results suggest that increased proteolytic maturation of NODAL potentiates autocrine signaling, whereas increased NODAL stability extends paracrine signaling.
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NODAL signaling in vertebrate development.
Annual review of cell and developmental biology, 2003Co-Authors: Alexander F. SchierAbstract:▪ Abstract TGFs signals belonging to the NODAL family set up the embryonic axes, induce mesoderm and endoderm, pattern the nervous system, and determine left-right asymmetry in vertebrates. NODAL signaling activates a canonical TGFs pathway involving activin receptors, Smad2 transcription factors, and FoxH1 coactivators. In addition, NODAL signaling is dependent on coreceptors of the EGF-CFC family and antagonized by the Lefty and Cerberus families of secreted factors. Additional modulators of NODAL signaling include convertases that regulate the generation of the mature signal, and factors such as Arkadia and DRAP1 that regulate the cellular responses to the signal. Complex regulatory cascades and autoregulatory loops coordinate NODAL signaling during early development. NODALs have concentration-dependent roles and can act both locally and at a distance. These studies demonstrate that NODAL signaling is modulated at almost every level to precisely orchestrate tissue patterning during vertebrate embryogen...
Francisco Perezmontano - One of the best experts on this subject based on the ideXlab platform.
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the non flavonoid inducible noda3 and the flavonoid regulated noda1 genes of rhizobium tropici ciat 899 guarantee nod factor production and nodulation of different host legumes
Plant and Soil, 2019Co-Authors: Pablo Del Cerro, Manuel Megias, Antonio M Gilserrano, Paula Ayalagarcia, Irene Jimenezguerrero, Francisco Javier Lopezbaena, Jose Maria Vinardell, Mariangela Hungria, Francisco PerezmontanoAbstract:The symbiosis between rhizobia and their host legumes is initiated by a complex molecular dialogue in which the activation of bacterial NodD proteins by appropriate plant flavonoids triggers the expression of the bacterial nodulation (nod) genes. These genes are involved in the synthesis and export of the Nodulation factors (NF), which are signal molecules that, when recognized by plant receptors, launch the symbiotic process. The core of NF is synthesized by proteins encoded by the nodABC genes, whereas the rest of the nod genes protein products are involved in the decoration of NF with different chemical substituents and their export to the environment. Rhizobium tropici CIAT 899, the microsymbiont of common bean (Phaseolus vulgaris), is characterized for tolerating multiple physical stresses and for synthesizing a large variety of NF not only in the presence of inducing flavonoids but also when high concentrations of salt are present. In addition, another interesting feature of the R. tropici CIAT 899 genome is the presence of three different nodA genes on the symbiotic plasmid, although their exact roles remain to be elucidated. In this work, we characterize the role of the three NodA proteins of R. tropici CIAT 899 in symbiosis. We have analyzed by quantitative PCR the expression of the nodA1, nodA2 and nodA3 genes of CIAT 899, showing that only nodA1 and nodA2 are inducible by flavonoids. We have also constructed single, double and triple non-polar mutants in these genes in order to study their importance in NF production and in nodulation of four different host legumes of CIAT 899: P. vulgaris, Leucaena leucocephala, Lotus japonicus, and L. burttii. The nodA1 and nodA2 genes of CIAT 899 (both inducible by flavonoids) are more related between them than with nodA3 (non-flavonoid inducible). Interestingly, the presence of NodA1 or NodA3 is crucial for nodulation with L. leucocephala and L. japonicus, since both NodA1 or NodA3 guarantee Nod factor production upon apigenin induction. Interestingly, osmotic-stressing conditions increase the quantity and diversity of the Nod factors synthesized by NodA2, being these molecules able to induce the formation of nodule primordia on P. vulgaris. We concluded that R. tropici CIAT 899 requires at least the flavonoid-induced nodA1 or the flavonoid-independent nodA3 genes for ensuring symbiotic success in the four assayed host-legumes. The inducible nodA2 gene is sufficient to induce nodulation on P. vulgaris and L. burttii but not in L. leucocephala and L. japonicus. To our knowledge, in this work we report for the first time that a non-flavonoid inducible copy of nodA is enough to induce nodulation on legumes.
Ali H Brivanlou - One of the best experts on this subject based on the ideXlab platform.
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the mir 430 427 302 family controls mesendodermal fate specification via species specific target selection
Developmental Cell, 2009Co-Authors: Alessandro Rosa, Francesca M Spagnoli, Ali H BrivanlouAbstract:The role of microRNAs in embryonic cell fate specification is largely unknown. In vertebrates, the miR-430/427/302 family shows a unique expression signature and is exclusively expressed during early embryogenesis. Here, we comparatively address the embryonic function of miR-302 in human embryonic stem cells (hESCs) and its ortholog miR-427 in Xenopus laevis. Interestingly, we found that this miRNA family displays species-specific target selection among ligands of the NODAL pathway, with a striking conservation of the inhibitors, Lefties, but differential targeting of the activators, NODALs. The NODAL pathway plays a crucial role in germ layer specification. Accordingly, by gain and loss of function experiments in hESCs, we show that miR-302 promotes the mesendodermal lineage at the expense of neuroectoderm formation. Similarly, depletion of miR-427 in Xenopus embryos hinders the organizer formation and leads to severe dorsal mesodermal patterning defects. These findings suggest a crucial role for the miR-430/427/302 family in vertebrate embryogenesis by controlling germ layer specification.
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the orphan receptor alk7 and the activin receptor alk4 mediate signaling by NODAL proteins during vertebrate development
Genes & Development, 2001Co-Authors: Eva Reissmann, Gabriella Minchiotti, Hans Jörnvall, Andries Blokzijl, Olov Andersson, Chenbei Chang, Graziella M Persico, Carlos F Ibanez, Ali H BrivanlouAbstract:NODAL proteins have crucial roles in mesendoderm formation and left–right patterning during vertebrate development. The molecular mechanisms of signal transduction by NODAL and related ligands, however, are not fully understood. In this paper, we present biochemical and functional evidence that the orphan type I serine/threonine kinase receptor ALK7 acts as a receptor for mouse NODAL and Xenopus NODAL-related 1 (Xnr1). Receptor reconstitution experiments indicate that ALK7 collaborates with ActRIIB to confer responsiveness to Xnr1 and NODAL. Both receptors can independently bind Xnr1. In addition, Cripto, an extracellular protein genetically implicated in NODAL signaling, can independently interact with both Xnr1 and ALK7, and its expression greatly enhances the ability of ALK7 and ActRIIB to respond to NODAL ligands. The Activin receptor ALK4 is also able to mediate NODAL signaling but only in the presence of Cripto, with which it can also interact directly. A constitutively activated form of ALK7 mimics the mesendoderm-inducing activity of Xnr1 in Xenopus embryos, whereas a dominant-negative ALK7 specifically blocks the activities of NODAL and Xnr1 but has little effect on other related ligands. In contrast, a dominant-negative ALK4 blocks all mesoderm-inducing ligands tested, including NODAL, Xnr1, Xnr2, Xnr4, and Activin. In agreement with a role in NODAL signaling, ALK7 mRNA is localized to the ectodermal and organizer regions of Xenopus gastrula embryos and is expressed during early stages of mouse embryonic development. Therefore, our results indicate that both ALK4 and ALK7 can mediate signal transduction by NODAL proteins, although ALK7 appears to be a receptor more specifically dedicated to NODAL signaling.
Irene Jimenezguerrero - One of the best experts on this subject based on the ideXlab platform.
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the non flavonoid inducible noda3 and the flavonoid regulated noda1 genes of rhizobium tropici ciat 899 guarantee nod factor production and nodulation of different host legumes
Plant and Soil, 2019Co-Authors: Pablo Del Cerro, Manuel Megias, Antonio M Gilserrano, Paula Ayalagarcia, Irene Jimenezguerrero, Francisco Javier Lopezbaena, Jose Maria Vinardell, Mariangela Hungria, Francisco PerezmontanoAbstract:The symbiosis between rhizobia and their host legumes is initiated by a complex molecular dialogue in which the activation of bacterial NodD proteins by appropriate plant flavonoids triggers the expression of the bacterial nodulation (nod) genes. These genes are involved in the synthesis and export of the Nodulation factors (NF), which are signal molecules that, when recognized by plant receptors, launch the symbiotic process. The core of NF is synthesized by proteins encoded by the nodABC genes, whereas the rest of the nod genes protein products are involved in the decoration of NF with different chemical substituents and their export to the environment. Rhizobium tropici CIAT 899, the microsymbiont of common bean (Phaseolus vulgaris), is characterized for tolerating multiple physical stresses and for synthesizing a large variety of NF not only in the presence of inducing flavonoids but also when high concentrations of salt are present. In addition, another interesting feature of the R. tropici CIAT 899 genome is the presence of three different nodA genes on the symbiotic plasmid, although their exact roles remain to be elucidated. In this work, we characterize the role of the three NodA proteins of R. tropici CIAT 899 in symbiosis. We have analyzed by quantitative PCR the expression of the nodA1, nodA2 and nodA3 genes of CIAT 899, showing that only nodA1 and nodA2 are inducible by flavonoids. We have also constructed single, double and triple non-polar mutants in these genes in order to study their importance in NF production and in nodulation of four different host legumes of CIAT 899: P. vulgaris, Leucaena leucocephala, Lotus japonicus, and L. burttii. The nodA1 and nodA2 genes of CIAT 899 (both inducible by flavonoids) are more related between them than with nodA3 (non-flavonoid inducible). Interestingly, the presence of NodA1 or NodA3 is crucial for nodulation with L. leucocephala and L. japonicus, since both NodA1 or NodA3 guarantee Nod factor production upon apigenin induction. Interestingly, osmotic-stressing conditions increase the quantity and diversity of the Nod factors synthesized by NodA2, being these molecules able to induce the formation of nodule primordia on P. vulgaris. We concluded that R. tropici CIAT 899 requires at least the flavonoid-induced nodA1 or the flavonoid-independent nodA3 genes for ensuring symbiotic success in the four assayed host-legumes. The inducible nodA2 gene is sufficient to induce nodulation on P. vulgaris and L. burttii but not in L. leucocephala and L. japonicus. To our knowledge, in this work we report for the first time that a non-flavonoid inducible copy of nodA is enough to induce nodulation on legumes.
Yuji Yokouchi - One of the best experts on this subject based on the ideXlab platform.
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multi modal effects of bmp signaling on NODAL expression in the lateral plate mesoderm during left right axis formation in the chick embryo
Developmental Biology, 2013Co-Authors: Kenjiro Katsu, Norifumi Tatsumi, Daisuke Niki, Ken Ichi Yamamura, Yuji YokouchiAbstract:Abstract During development of left–right asymmetry in the vertebrate embryo, NODAL plays a central role for determination of left-handedness. Bone morphogenetic protein (BMP) signaling has an important role for regulation of NODAL expression, although there is controversy over whether BMP signaling has a positive or negative effect on NODAL expression in the chick embryo. As BMP is a morphogen, we speculated that different concentrations might induce different responses in the cells of the lateral plate mesoderm (LPM). To test this hypothesis, we analyzed the effects of various concentrations of BMP4 and NOGGIN on NODAL expression in the LPM. We found that the effect on NODAL expression varied in a complex fashion with the concentration of BMP. In agreement with previous reports, we found that a high level of BMP signaling induced NODAL expression in the LPM, whereas a low level inhibited expression. However, a high intermediate level of BMP signaling was found to suppress NODAL expression in the left LPM, whereas a low intermediate level induced NODAL expression in the right LPM. Thus, the high and the low intermediate levels of BMP signaling up-regulated NODAL expression, but the high intermediate and low levels of BMP signaling down-regulated NODAL expression. Next, we sought to identify the mechanisms of this complex regulation of NODAL expression by BMP signaling. At the low intermediate level of BMP signaling, regulation depended on a NODAL positive-feedback loop suggesting the possibility of crosstalk between BMP and NODAL signaling. Overexpression of a constitutively active BMP receptor, a constitutively active ACTIVIN/NODAL receptor and SMAD4 indicated that SMAD1 and SMAD2 competed for binding to SMAD4 in the cells of the LPM. NODAL regulation by the high and low levels of BMP signaling was dependent on Cfc up-regulation or down-regulation, respectively. We propose a model for the variable effects of BMP signaling on NODAL expression in which different levels of BMP signaling regulate NODAL expression by a balance between BMP-pSMAD1/4 signaling and NODAL-pSMAD2/4 signaling.
