The Experts below are selected from a list of 15339 Experts worldwide ranked by ideXlab platform
Clifford J Tabin - One of the best experts on this subject based on the ideXlab platform.
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Sonic Hedgehog differentially regulates expression of gli and gli3 during limb development
Developmental Biology, 1996Co-Authors: Valeria Marigo, Randy L. Johnson, Andrea Vortkamp, Clifford J TabinAbstract:Abstract Sonic Hedgehog is a secreted factor regulating patterning of the anterior–posterior axis in the developing limb. The signaling pathway mediating the transduction of the signal is still poorly understood. InDrosophilaseveral genes are known to act downstream ofHedgehog,the fly homolog ofSonic Hedgehog.An important gene epistatic toHedgehogiscubitus interruptus,which encodes the fly homolog of a family of vertebrate putative transcription factors, theGLIgenes. We have isolated two members of theGLIfamily from chick, calledGLIandGLI3.Their expression patterns in a variety of tissues during embryogenesis suggest that these genes may be targets of the Sonic Hedgehog signal. We demonstrate that the twoGLIgenes are differentially regulated by Sonic Hedgehog during limb development. Sonic Hedgehog up-regulatesGLItranscription, while down-regulatingGLI3expression in the mesenchymal cells of the developing limb bud. Finally, we demonstrate that an activated form of GLI can induce expression ofPatched,a known target of Sonic Hedgehog, thus implicating GLI as a key transcription factor in the vertebrate Hedgehog signaling pathway. In conjunction with evidence from a mouseGli3mutant, our data suggest that GLI and GLI3 may have taken two different functions of theirDrosophilahomologcubitus interruptus.
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regulation of patched by Sonic Hedgehog in the developing neural tube
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Valeria Marigo, Clifford J TabinAbstract:Abstract Ventral cell fates in the central nervous system are induced by Sonic Hedgehog, a homolog of Hedgehog, a secreted Drosophila protein. In the central nervous system, Sonic Hedgehog has been identified as the signal inducing floor plate, motor neurons, and dopaminergic neurons. Sonic Hedgehog is also involved in the induction of ventral cell type in the developing somites. ptc is a key gene in the Drosophila Hedgehog signaling pathway where it is involved in transducing the Hedgehog signal and is also a transcriptional target of the signal. PTC, a vertebrate homolog of this Drosophila gene, is genetically downstream of Sonic Hedgehog (Shh) in the limb bud. We analyze PTC expression during chicken neural and somite development and find it expressed in all regions of these tissues known to be responsive to Sonic Hedgehog signal. As in the limb bud, ectopic expression of Sonic Hedgehog leads to ectopic induction of PTC in the neural tube and paraxial mesoderm. This conservation of regulation allows us to use PTC as a marker for Sonic Hedgehog response. The pattern of PTC expression suggests that Sonic Hedgehog may play an inductive role in more dorsal regions of the neural tube than have been previously demonstrated. Examination of the pattern of PTC expression also suggests that PTC may act in a negative feedback loop to attenuate Hedgehog signaling.
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conservation in Hedgehog signaling induction of a chicken patched homolog by Sonic Hedgehog in the developing limb
Development, 1996Co-Authors: Valeria Marigo, Ronald L Johnson, Matthew P Scott, Lisa V Goodrich, Clifford J TabinAbstract:Hedgehog genes have been implicated in inductive signaling during development in a variety of organisms. A key element of the Hedgehog signaling system is encoded by the gene patched. In Drosophila Hedgehog regulates gene expression by antagonizing the action of patched. In addition, patched is itself a transcriptional target of Hedgehog signaling. We have isolated a chicken patched homolog and find it to be strongly expressed adjacent to all tissues where members of the Hedgehog family are expressed. As in Drosophila, ectopic expression of Sonic Hedgehog leads to ectopic induction of chicken Patched. Based on this regulatory conservation, vertebrate Patched is likely to be directly downstream of Sonic Hedgehog signaling. An important role of Sonic Hedgehog is the regulation of anterior/posterior pattern in the developing limb bud. Since Patched is directly downstream of the Hedgehog signal, the extent of high level Patched expression provides a measure of the distance that Sonic Hedgehog diffuses and directly acts. On this basis, we find that Sonic Hedgehog directly acts as a signal over only the posterior third of the limb bud. During limb patterning, secondary signals are secreted in both the mesoderm (e.g. Bone Morphogenetic Protein-2) and apical ectodermal ridge (e.g. Fibroblast Growth Factor-4) in response to Sonic Hedgehog. Thus knowing which is the direct target tissue is essential for unraveling the molecular patterning of the limb. The expression of Patched provides a strong indication that the mesoderm and not the ectoderm is the direct target of Sonic Hedgehog signaling in the limb bud. Finally we demonstrate that induction of Patched requires Sonic Hedgehog but, unlike Bone Morphogenetic Protein-2 and Hox genes, does not require Fibroblast Growth Factor as a co-inducer. It is therefore a more direct target of Sonic Hedgehog than previously reported patterning genes.
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Sonic Hedgehog and fgf 4 act through a signaling cascade and feedback loop to integrate growth and patterning of the developing limb bud
Cell, 1994Co-Authors: Ed Laufer, Randy L. Johnson, Craig E Nelson, Bruce A Morgan, Clifford J TabinAbstract:Proper limb growth and patterning requires signals from the zone of polarizing activity in the posterior mesoderm and from the overlying apical ectodermal ridge (AER). Sonic Hedgehog and Fgf-4, respectively, have recently been identified as candidates for these signals. We have dissected the roles of these secreted proteins in early limb development by ectopically regulating their activities in a number of surgical contexts. Our results indicate that Sonic Hedgehog initiates expression of secondary signaling molecules, including Bmp-2 in the mesoderm and Fgf-4 in the ectoderm. The mesoderm requires ectodermally derived competence factors, which include Fgf-4, to activate target gene expression in response to Sonic Hedgehog. The expression of Sonic Hedgehog and Fgf-4 is coordinately regulated by a positive feedback loop operating between the posterior mesoderm and the overlying AER. Taken together, these data provide a basis for understanding the integration of growth and patterning in the developing limb.
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Sonic Hedgehog mediates the polarizing activity of the zpa
Cell, 1993Co-Authors: Robert D. Riddle, Randy L. Johnson, Ed Laufer, Clifford J TabinAbstract:The zone of polarizing activity (ZPA) is a region at the posterior margin of the limb bud that induces mirror-image duplications when grafted to the anterior of a second limb. We have isolated a vertebrate gene, Sonic Hedgehog, related to the Drosophila segment polarity gene Hedgehog, which is expressed specifically in the ZPA and in other regions of the embryo, that is capable of polarizing limbs in grafting experiments. Retinoic acid, which can convert anterior limb bud tissue into tissue with polarizing activity, concomitantly induces Sonic Hedgehog expression in the anterior limb bud. Implanting cells that express Sonic Hedgehog into anterior limb buds is sufficient to cause ZPA-like limb duplications. Like the ZPA, Sonic Hedgehog expression leads to the activation of Hox genes. Sonic Hedgehog thus appears to function as the signal for antero-posterior patterning in the limb.
Yves Boucher - One of the best experts on this subject based on the ideXlab platform.
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Could an endoneurial endothelial crosstalk between Wnt/β-catenin and Sonic Hedgehog pathways underlie the early disruption of the infraorbital blood–nerve barrier following chronic constriction injury?
Molecular Pain, 2017Co-Authors: Nathan Moreau, Annie Mauborgne, Pierre-olivier Couraud, Ignacio A Romero, Babette B Weksler, Luis Villanueva, Michel Pohl, Yves BoucherAbstract:Background: Blood–nerve barrier disruption is pivotal in the development of neuroinflammation, peripheral sensitization, and neuropathic pain after peripheral nerve injury. Activation of toll-like receptor 4 and inactivation of Sonic Hedgehog signaling pathways within the endoneurial endothelial cells are key events, resulting in the infiltration of harmful molecules and immunocytes within the nerve parenchyma. However, we showed in a previous study that preemptive inactivation of toll-like receptor 4 signaling or sustained activation of Sonic Hedgehog signaling did not prevent the local alterations observed following peripheral nerve injury, suggesting the implication of another signaling pathway. Methods: Using a classical neuropathic pain model, the infraorbital nerve chronic constriction injury (IoN-CCI), we investigated the role of the Wnt/β-catenin pathway in chronic constriction injury-mediated blood–nerve barrier disruption and in its interactions with the toll-like receptor 4 and Sonic Hedgehog pathways. In the IoN-CCI model versus control, mRNA expression levels and/or immunochemical detection of major Wnt/Sonic Hedgehog pathway (Frizzled-7, vascular endothelial-cadherin, Patched-1 and Gli-1) and/or tight junction proteins (Claudin-1, Claudin-5, and Occludin) readouts were assessed. Vascular permeability was assessed by sodium fluorescein extravasation. Results: IoN-CCI induced early alterations in the vascular endothelial-cadherin/β-catenin/Frizzled-7 complex, shown to participate in local blood–nerve barrier disruption via a β-catenin-dependent tight junction protein downregulation. Wnt pathway also mediated a crosstalk between toll-like receptor 4 and Sonic Hedgehog signaling within endoneurial endothelial cells. Nevertheless, preemptive inhibition of Wnt/β-catenin signaling before IoN-CCI could not prevent the downregulation of key Sonic Hedgehog pathway readouts or the disruption of the infraorbital blood–nerve barrier, suggesting that Sonic Hedgehog pathway inhibition observed following IoN-CCI is an independent event responsible for blood–nerve barrier disruption. Conclusion: A crosstalk between Wnt/β-catenin- and Sonic Hedgehog-mediated signaling pathways within endoneurial endothelial cells could mediate the chronic disruption of the blood–nerve barrier following IoN-CCI, resulting in increased irreversible endoneurial vascular permeability and neuropathic pain development.
Zheng Gang Zhang - One of the best experts on this subject based on the ideXlab platform.
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Sonic Hedgehog signaling pathway mediates cerebrolysin improved neurological function after stroke
Stroke, 2013Co-Authors: Li Zhang, Michael Chopp, Yisheng Cui, Lei Wang, Alexandra Szalad, Stefan Winter, Dieter Meier, Min Wei, Zheng Gang ZhangAbstract:Background and Purpose—Cerebrolysin, a mixture of neurotrophic peptides, enhances neurogenesis and improves neurological outcome in experimental neurodegenerative diseases and stroke. The Sonic Hedgehog (Shh) signaling pathway stimulates neurogenesis after stroke. The present study tests whether the Shh pathway mediates cerebrolysin-induced neurogenesis and improves neurological outcome after stroke. Methods—Rats subjected to embolic stroke were treated with cerebrolysin with or without cyclopamine. Results—Using neural progenitor cells derived from the subventricular zone of the lateral ventricle of adult rats, we found that cerebrolysin significantly increased neural progenitor cells proliferation and their differentiation into neurons and myelinating oligodendrocytes, which were associated with upregulation of Shh and its receptors patched and smoothened. Blockage of the Shh signaling pathway with a pharmacological smoothened inhibitor, cyclopamine, abolished cerebrolysin-induced in vitro neurogenesis ...
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Abstract WMP36: The Sonic Hedgehog Signaling Pathway Mediates Cerebrolysin-Improved Neurological Functions after Stroke
Stroke, 2013Co-Authors: Li Zhang, Michael Chopp, Zheng Gang ZhangAbstract:Cerebrolysin, a mixture of neurotrophic peptides, enhances neurogenesis in experimental neurodegenerative diseases and stroke. Sonic Hedgehog (Shh) signaling pathway stimulates neurogenesis after s...
Alex F Chen - One of the best experts on this subject based on the ideXlab platform.
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thrombospondin 1 cd36 pathway contributes to bone marrow derived angiogenic cell dysfunction in type 1 diabetes via Sonic Hedgehog pathway suppression
American Journal of Physiology-endocrinology and Metabolism, 2013Co-Authors: Jiemei Wang, Jeffery S Isenberg, Timothy R Billiar, Alex F ChenAbstract:Refractory wounds in diabetic patients present a significant clinical problem. Sonic Hedgehog (SHH), a morphogenic protein central to wound repair, is deficient in diabetes. Regulation of SHH in wo...
Valeria Marigo - One of the best experts on this subject based on the ideXlab platform.
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Sonic Hedgehog differentially regulates expression of gli and gli3 during limb development
Developmental Biology, 1996Co-Authors: Valeria Marigo, Randy L. Johnson, Andrea Vortkamp, Clifford J TabinAbstract:Abstract Sonic Hedgehog is a secreted factor regulating patterning of the anterior–posterior axis in the developing limb. The signaling pathway mediating the transduction of the signal is still poorly understood. InDrosophilaseveral genes are known to act downstream ofHedgehog,the fly homolog ofSonic Hedgehog.An important gene epistatic toHedgehogiscubitus interruptus,which encodes the fly homolog of a family of vertebrate putative transcription factors, theGLIgenes. We have isolated two members of theGLIfamily from chick, calledGLIandGLI3.Their expression patterns in a variety of tissues during embryogenesis suggest that these genes may be targets of the Sonic Hedgehog signal. We demonstrate that the twoGLIgenes are differentially regulated by Sonic Hedgehog during limb development. Sonic Hedgehog up-regulatesGLItranscription, while down-regulatingGLI3expression in the mesenchymal cells of the developing limb bud. Finally, we demonstrate that an activated form of GLI can induce expression ofPatched,a known target of Sonic Hedgehog, thus implicating GLI as a key transcription factor in the vertebrate Hedgehog signaling pathway. In conjunction with evidence from a mouseGli3mutant, our data suggest that GLI and GLI3 may have taken two different functions of theirDrosophilahomologcubitus interruptus.
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regulation of patched by Sonic Hedgehog in the developing neural tube
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Valeria Marigo, Clifford J TabinAbstract:Abstract Ventral cell fates in the central nervous system are induced by Sonic Hedgehog, a homolog of Hedgehog, a secreted Drosophila protein. In the central nervous system, Sonic Hedgehog has been identified as the signal inducing floor plate, motor neurons, and dopaminergic neurons. Sonic Hedgehog is also involved in the induction of ventral cell type in the developing somites. ptc is a key gene in the Drosophila Hedgehog signaling pathway where it is involved in transducing the Hedgehog signal and is also a transcriptional target of the signal. PTC, a vertebrate homolog of this Drosophila gene, is genetically downstream of Sonic Hedgehog (Shh) in the limb bud. We analyze PTC expression during chicken neural and somite development and find it expressed in all regions of these tissues known to be responsive to Sonic Hedgehog signal. As in the limb bud, ectopic expression of Sonic Hedgehog leads to ectopic induction of PTC in the neural tube and paraxial mesoderm. This conservation of regulation allows us to use PTC as a marker for Sonic Hedgehog response. The pattern of PTC expression suggests that Sonic Hedgehog may play an inductive role in more dorsal regions of the neural tube than have been previously demonstrated. Examination of the pattern of PTC expression also suggests that PTC may act in a negative feedback loop to attenuate Hedgehog signaling.
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conservation in Hedgehog signaling induction of a chicken patched homolog by Sonic Hedgehog in the developing limb
Development, 1996Co-Authors: Valeria Marigo, Ronald L Johnson, Matthew P Scott, Lisa V Goodrich, Clifford J TabinAbstract:Hedgehog genes have been implicated in inductive signaling during development in a variety of organisms. A key element of the Hedgehog signaling system is encoded by the gene patched. In Drosophila Hedgehog regulates gene expression by antagonizing the action of patched. In addition, patched is itself a transcriptional target of Hedgehog signaling. We have isolated a chicken patched homolog and find it to be strongly expressed adjacent to all tissues where members of the Hedgehog family are expressed. As in Drosophila, ectopic expression of Sonic Hedgehog leads to ectopic induction of chicken Patched. Based on this regulatory conservation, vertebrate Patched is likely to be directly downstream of Sonic Hedgehog signaling. An important role of Sonic Hedgehog is the regulation of anterior/posterior pattern in the developing limb bud. Since Patched is directly downstream of the Hedgehog signal, the extent of high level Patched expression provides a measure of the distance that Sonic Hedgehog diffuses and directly acts. On this basis, we find that Sonic Hedgehog directly acts as a signal over only the posterior third of the limb bud. During limb patterning, secondary signals are secreted in both the mesoderm (e.g. Bone Morphogenetic Protein-2) and apical ectodermal ridge (e.g. Fibroblast Growth Factor-4) in response to Sonic Hedgehog. Thus knowing which is the direct target tissue is essential for unraveling the molecular patterning of the limb. The expression of Patched provides a strong indication that the mesoderm and not the ectoderm is the direct target of Sonic Hedgehog signaling in the limb bud. Finally we demonstrate that induction of Patched requires Sonic Hedgehog but, unlike Bone Morphogenetic Protein-2 and Hox genes, does not require Fibroblast Growth Factor as a co-inducer. It is therefore a more direct target of Sonic Hedgehog than previously reported patterning genes.
