FGF8 and SHH substitute for anterior–posterior tissue interactions to induce limb regeneration View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-05

AUTHORS

Eugeniu Nacu, Elena Gromberg, Catarina R. Oliveira, David Drechsel, Elly M. Tanaka

ABSTRACT

In salamanders, grafting of a left limb blastema onto a right limb stump yields regeneration of three limbs, the normal limb and two 'supernumerary' limbs. This experiment and other research have shown that the juxtaposition of anterior and posterior limb tissue plus innervation are necessary and sufficient to induce complete limb regeneration in salamanders. However, the cellular and molecular basis of the requirement for anterior-posterior tissue interactions were unknown. Here we have clarified the molecular basis of the requirement for both anterior and posterior tissue during limb regeneration and supernumerary limb formation in axolotls (Ambystoma mexicanum). We show that the two tissues provide complementary cross-inductive signals that are required for limb outgrowth. A blastema composed solely of anterior tissue normally regresses rather than forming a limb, but activation of hedgehog (HH) signalling was sufficient to drive regeneration of an anterior blastema to completion owing to its ability to maintain fibroblast growth factor (FGF) expression, the key signalling activity responsible for blastema outgrowth. In blastemas composed solely of posterior tissue, HH signalling was not sufficient to drive regeneration; however, ectopic expression of FGF8 together with endogenous HH signalling was sufficient. In axolotls, FGF8 is expressed only in the anterior mesenchyme and maintenance of its expression depends on sonic hedgehog (SHH) signalling from posterior tissue. Together, our findings identify key anteriorly and posteriorly localized signals that promote limb regeneration and show that these single factors are sufficient to drive non-regenerating blastemas to complete regeneration with full elaboration of skeletal elements. More... »

PAGES

407

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature17972

DOI

http://dx.doi.org/10.1038/nature17972

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043550165

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27120163


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biochemistry and Cell Biology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Ambystoma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Body Patterning", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Choristoma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Extremities", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Fibroblast Growth Factor 8", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Hedgehog Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mesoderm", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Regeneration", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Signal Transduction", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Max Planck Institute of Molecular Cell Biology and Genetics", 
          "id": "https://www.grid.ac/institutes/grid.419537.d", 
          "name": [
            "DFG Research Center for Regenerative Therapies, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany", 
            "Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Nacu", 
        "givenName": "Eugeniu", 
        "id": "sg:person.0640374752.48", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0640374752.48"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Max Planck Institute of Molecular Cell Biology and Genetics", 
          "id": "https://www.grid.ac/institutes/grid.419537.d", 
          "name": [
            "DFG Research Center for Regenerative Therapies, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany", 
            "Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gromberg", 
        "givenName": "Elena", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Porto", 
          "id": "https://www.grid.ac/institutes/grid.5808.5", 
          "name": [
            "DFG Research Center for Regenerative Therapies, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany", 
            "Graduate Program in Areas of Basic and Applied Biology, Abel Salazar Biomedical Sciences Institute, University of Porto, 4099-003 Porto, Portugal"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Oliveira", 
        "givenName": "Catarina R.", 
        "id": "sg:person.015613460740.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015613460740.02"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Max Planck Institute of Molecular Cell Biology and Genetics", 
          "id": "https://www.grid.ac/institutes/grid.419537.d", 
          "name": [
            "Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Drechsel", 
        "givenName": "David", 
        "id": "sg:person.0760526157.49", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0760526157.49"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Max Planck Institute of Molecular Cell Biology and Genetics", 
          "id": "https://www.grid.ac/institutes/grid.419537.d", 
          "name": [
            "DFG Research Center for Regenerative Therapies, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany", 
            "Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Tanaka", 
        "givenName": "Elly M.", 
        "id": "sg:person.01021663747.70", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01021663747.70"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1006/dbio.2001.0346", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001587048"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1242/dev.02529", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005841899"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ydbio.2007.09.021", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005954097"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.93.6.2348", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008863055"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0012-1606(75)90381-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012233613"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/263676a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012312874", 
          "https://doi.org/10.1038/263676a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/44157", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012355245", 
          "https://doi.org/10.1038/44157"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/44157", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012355245", 
          "https://doi.org/10.1038/44157"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature06718", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012554580", 
          "https://doi.org/10.1038/nature06718"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature06876", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018542411", 
          "https://doi.org/10.1038/nature06876"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng1178", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019185949", 
          "https://doi.org/10.1038/ng1178"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng1178", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019185949", 
          "https://doi.org/10.1038/ng1178"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2004.07.024", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021280382"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ydbio.2005.11.037", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021699873"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ydbio.2004.02.016", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028241851"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0092-8674(94)90030-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028497067"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/82601", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029988663", 
          "https://doi.org/10.1038/82601"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/82601", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029988663", 
          "https://doi.org/10.1038/82601"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/286803a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031081679", 
          "https://doi.org/10.1038/286803a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.devcel.2008.01.008", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031150571"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0167-7799(01)01911-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032890492"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08152", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034361762", 
          "https://doi.org/10.1038/nature08152"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08152", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034361762", 
          "https://doi.org/10.1038/nature08152"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ydbio.2006.05.026", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034988058"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1242/dev.01906", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035425867"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/371609a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037221662", 
          "https://doi.org/10.1038/371609a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1242/dev.081752", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042389659"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.gt.3302657", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044765773", 
          "https://doi.org/10.1038/sj.gt.3302657"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.gt.3302657", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044765773", 
          "https://doi.org/10.1038/sj.gt.3302657"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev-cellbio-092910-154115", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050815305"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jez.1402040302", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051817183"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jez.1402040302", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051817183"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/82609", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053535235", 
          "https://doi.org/10.1038/82609"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/82609", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053535235", 
          "https://doi.org/10.1038/82609"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/icb/22.1.131", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059652625"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.212.4498.993", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062523140"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.644323", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062637613"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2144/000113238", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069096074"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1081868961", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082180968", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2016-05", 
    "datePublishedReg": "2016-05-01", 
    "description": "In salamanders, grafting of a left limb blastema onto a right limb stump yields regeneration of three limbs, the normal limb and two 'supernumerary' limbs. This experiment and other research have shown that the juxtaposition of anterior and posterior limb tissue plus innervation are necessary and sufficient to induce complete limb regeneration in salamanders. However, the cellular and molecular basis of the requirement for anterior-posterior tissue interactions were unknown. Here we have clarified the molecular basis of the requirement for both anterior and posterior tissue during limb regeneration and supernumerary limb formation in axolotls (Ambystoma mexicanum). We show that the two tissues provide complementary cross-inductive signals that are required for limb outgrowth. A blastema composed solely of anterior tissue normally regresses rather than forming a limb, but activation of hedgehog (HH) signalling was sufficient to drive regeneration of an anterior blastema to completion owing to its ability to maintain fibroblast growth factor (FGF) expression, the key signalling activity responsible for blastema outgrowth. In blastemas composed solely of posterior tissue, HH signalling was not sufficient to drive regeneration; however, ectopic expression of FGF8 together with endogenous HH signalling was sufficient. In axolotls, FGF8 is expressed only in the anterior mesenchyme and maintenance of its expression depends on sonic hedgehog (SHH) signalling from posterior tissue. Together, our findings identify key anteriorly and posteriorly localized signals that promote limb regeneration and show that these single factors are sufficient to drive non-regenerating blastemas to complete regeneration with full elaboration of skeletal elements. ", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/nature17972", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1018957", 
        "issn": [
          "0090-0028", 
          "1476-4687"
        ], 
        "name": "Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "7603", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "533"
      }
    ], 
    "name": "FGF8 and SHH substitute for anterior\u2013posterior tissue interactions to induce limb regeneration", 
    "pagination": "407", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "cf71f785b5b340e5bca8578b487beb51d5c59541e4a3e4d31195d146ef6588fa"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "27120163"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "0410462"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/nature17972"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1043550165"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/nature17972", 
      "https://app.dimensions.ai/details/publication/pub.1043550165"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T19:45", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8681_00000426.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/nature17972"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature17972'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature17972'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature17972'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature17972'


 

This table displays all metadata directly associated to this object as RDF triples.

249 TRIPLES      21 PREDICATES      72 URIs      31 LITERALS      19 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/nature17972 schema:about N23a6a784467e44b7b6cfd2eda6caeb59
2 N265ac903699e4c81acb303791e8cc6a3
3 N3198d9599b5b45938db28aa06e21ac5c
4 N31ad10338f834a5e81160a5189979d94
5 N50ca22db04f1406682b6f0605a42f5d8
6 N69a5d8f7040e47bdafe640e27168063b
7 Na74996ed091841d69476148cc87eb1b9
8 Nbb7231a3c4474119ad51a2ab08a7ec01
9 Nd3eef957155f430db88aaa52651fff8f
10 Ne03c55aaf8d74e718ead55726fd23dd5
11 anzsrc-for:06
12 anzsrc-for:0601
13 schema:author Nb2cb59e8989943ba8d4a176a9a2fcfb4
14 schema:citation sg:pub.10.1038/263676a0
15 sg:pub.10.1038/286803a0
16 sg:pub.10.1038/371609a0
17 sg:pub.10.1038/44157
18 sg:pub.10.1038/82601
19 sg:pub.10.1038/82609
20 sg:pub.10.1038/nature06718
21 sg:pub.10.1038/nature06876
22 sg:pub.10.1038/nature08152
23 sg:pub.10.1038/ng1178
24 sg:pub.10.1038/sj.gt.3302657
25 https://app.dimensions.ai/details/publication/pub.1081868961
26 https://app.dimensions.ai/details/publication/pub.1082180968
27 https://doi.org/10.1002/jez.1402040302
28 https://doi.org/10.1006/dbio.2001.0346
29 https://doi.org/10.1016/0012-1606(75)90381-4
30 https://doi.org/10.1016/0092-8674(94)90030-2
31 https://doi.org/10.1016/j.cell.2004.07.024
32 https://doi.org/10.1016/j.devcel.2008.01.008
33 https://doi.org/10.1016/j.ydbio.2004.02.016
34 https://doi.org/10.1016/j.ydbio.2005.11.037
35 https://doi.org/10.1016/j.ydbio.2006.05.026
36 https://doi.org/10.1016/j.ydbio.2007.09.021
37 https://doi.org/10.1016/s0167-7799(01)01911-4
38 https://doi.org/10.1073/pnas.93.6.2348
39 https://doi.org/10.1093/icb/22.1.131
40 https://doi.org/10.1126/science.212.4498.993
41 https://doi.org/10.1126/science.644323
42 https://doi.org/10.1146/annurev-cellbio-092910-154115
43 https://doi.org/10.1242/dev.01906
44 https://doi.org/10.1242/dev.02529
45 https://doi.org/10.1242/dev.081752
46 https://doi.org/10.2144/000113238
47 schema:datePublished 2016-05
48 schema:datePublishedReg 2016-05-01
49 schema:description In salamanders, grafting of a left limb blastema onto a right limb stump yields regeneration of three limbs, the normal limb and two 'supernumerary' limbs. This experiment and other research have shown that the juxtaposition of anterior and posterior limb tissue plus innervation are necessary and sufficient to induce complete limb regeneration in salamanders. However, the cellular and molecular basis of the requirement for anterior-posterior tissue interactions were unknown. Here we have clarified the molecular basis of the requirement for both anterior and posterior tissue during limb regeneration and supernumerary limb formation in axolotls (Ambystoma mexicanum). We show that the two tissues provide complementary cross-inductive signals that are required for limb outgrowth. A blastema composed solely of anterior tissue normally regresses rather than forming a limb, but activation of hedgehog (HH) signalling was sufficient to drive regeneration of an anterior blastema to completion owing to its ability to maintain fibroblast growth factor (FGF) expression, the key signalling activity responsible for blastema outgrowth. In blastemas composed solely of posterior tissue, HH signalling was not sufficient to drive regeneration; however, ectopic expression of FGF8 together with endogenous HH signalling was sufficient. In axolotls, FGF8 is expressed only in the anterior mesenchyme and maintenance of its expression depends on sonic hedgehog (SHH) signalling from posterior tissue. Together, our findings identify key anteriorly and posteriorly localized signals that promote limb regeneration and show that these single factors are sufficient to drive non-regenerating blastemas to complete regeneration with full elaboration of skeletal elements.
50 schema:genre research_article
51 schema:inLanguage en
52 schema:isAccessibleForFree false
53 schema:isPartOf N31f5ddd1267b4ef5811b00afe29fe2ed
54 N9800d702e39f4d49b48f626ee913fad7
55 sg:journal.1018957
56 schema:name FGF8 and SHH substitute for anterior–posterior tissue interactions to induce limb regeneration
57 schema:pagination 407
58 schema:productId N9ea3be28b011462384e81f169b0d4f72
59 Na46ae727886844459166d33797eacb80
60 Na6de1c3eac114201b64bd3dbefb0e3e9
61 Nc21ba8c83bdc43de92ea485b51dd6169
62 Ne831bfa7db3a48a2a2df019a27a8b556
63 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043550165
64 https://doi.org/10.1038/nature17972
65 schema:sdDatePublished 2019-04-10T19:45
66 schema:sdLicense https://scigraph.springernature.com/explorer/license/
67 schema:sdPublisher N9a8b42d846ee459bb8e1f8db88518442
68 schema:url https://www.nature.com/articles/nature17972
69 sgo:license sg:explorer/license/
70 sgo:sdDataset articles
71 rdf:type schema:ScholarlyArticle
72 N1cf547bd84e84b219b598ef727749e14 rdf:first sg:person.01021663747.70
73 rdf:rest rdf:nil
74 N23a6a784467e44b7b6cfd2eda6caeb59 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
75 schema:name Mesoderm
76 rdf:type schema:DefinedTerm
77 N265ac903699e4c81acb303791e8cc6a3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
78 schema:name Signal Transduction
79 rdf:type schema:DefinedTerm
80 N2f7690ed3ba04ff8b3004dfa7a227820 rdf:first sg:person.015613460740.02
81 rdf:rest Ne5f8743988b445b4ba59cc95676083a5
82 N3198d9599b5b45938db28aa06e21ac5c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
83 schema:name Extremities
84 rdf:type schema:DefinedTerm
85 N31ad10338f834a5e81160a5189979d94 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
86 schema:name Fibroblast Growth Factor 8
87 rdf:type schema:DefinedTerm
88 N31f5ddd1267b4ef5811b00afe29fe2ed schema:volumeNumber 533
89 rdf:type schema:PublicationVolume
90 N50ca22db04f1406682b6f0605a42f5d8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
91 schema:name Ambystoma
92 rdf:type schema:DefinedTerm
93 N69a5d8f7040e47bdafe640e27168063b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
94 schema:name Regeneration
95 rdf:type schema:DefinedTerm
96 N9800d702e39f4d49b48f626ee913fad7 schema:issueNumber 7603
97 rdf:type schema:PublicationIssue
98 N9a8b42d846ee459bb8e1f8db88518442 schema:name Springer Nature - SN SciGraph project
99 rdf:type schema:Organization
100 N9ea3be28b011462384e81f169b0d4f72 schema:name pubmed_id
101 schema:value 27120163
102 rdf:type schema:PropertyValue
103 Na46ae727886844459166d33797eacb80 schema:name dimensions_id
104 schema:value pub.1043550165
105 rdf:type schema:PropertyValue
106 Na6de1c3eac114201b64bd3dbefb0e3e9 schema:name readcube_id
107 schema:value cf71f785b5b340e5bca8578b487beb51d5c59541e4a3e4d31195d146ef6588fa
108 rdf:type schema:PropertyValue
109 Na74996ed091841d69476148cc87eb1b9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
110 schema:name Animals
111 rdf:type schema:DefinedTerm
112 Nb1b8b40d0c3146599e3215c3b37d56de rdf:first Nd9d6939a3c384df892367eb83f0c3bd5
113 rdf:rest N2f7690ed3ba04ff8b3004dfa7a227820
114 Nb2cb59e8989943ba8d4a176a9a2fcfb4 rdf:first sg:person.0640374752.48
115 rdf:rest Nb1b8b40d0c3146599e3215c3b37d56de
116 Nbb7231a3c4474119ad51a2ab08a7ec01 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
117 schema:name Body Patterning
118 rdf:type schema:DefinedTerm
119 Nc21ba8c83bdc43de92ea485b51dd6169 schema:name doi
120 schema:value 10.1038/nature17972
121 rdf:type schema:PropertyValue
122 Nd3eef957155f430db88aaa52651fff8f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
123 schema:name Choristoma
124 rdf:type schema:DefinedTerm
125 Nd9d6939a3c384df892367eb83f0c3bd5 schema:affiliation https://www.grid.ac/institutes/grid.419537.d
126 schema:familyName Gromberg
127 schema:givenName Elena
128 rdf:type schema:Person
129 Ne03c55aaf8d74e718ead55726fd23dd5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
130 schema:name Hedgehog Proteins
131 rdf:type schema:DefinedTerm
132 Ne5f8743988b445b4ba59cc95676083a5 rdf:first sg:person.0760526157.49
133 rdf:rest N1cf547bd84e84b219b598ef727749e14
134 Ne831bfa7db3a48a2a2df019a27a8b556 schema:name nlm_unique_id
135 schema:value 0410462
136 rdf:type schema:PropertyValue
137 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
138 schema:name Biological Sciences
139 rdf:type schema:DefinedTerm
140 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
141 schema:name Biochemistry and Cell Biology
142 rdf:type schema:DefinedTerm
143 sg:journal.1018957 schema:issn 0090-0028
144 1476-4687
145 schema:name Nature
146 rdf:type schema:Periodical
147 sg:person.01021663747.70 schema:affiliation https://www.grid.ac/institutes/grid.419537.d
148 schema:familyName Tanaka
149 schema:givenName Elly M.
150 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01021663747.70
151 rdf:type schema:Person
152 sg:person.015613460740.02 schema:affiliation https://www.grid.ac/institutes/grid.5808.5
153 schema:familyName Oliveira
154 schema:givenName Catarina R.
155 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015613460740.02
156 rdf:type schema:Person
157 sg:person.0640374752.48 schema:affiliation https://www.grid.ac/institutes/grid.419537.d
158 schema:familyName Nacu
159 schema:givenName Eugeniu
160 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0640374752.48
161 rdf:type schema:Person
162 sg:person.0760526157.49 schema:affiliation https://www.grid.ac/institutes/grid.419537.d
163 schema:familyName Drechsel
164 schema:givenName David
165 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0760526157.49
166 rdf:type schema:Person
167 sg:pub.10.1038/263676a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012312874
168 https://doi.org/10.1038/263676a0
169 rdf:type schema:CreativeWork
170 sg:pub.10.1038/286803a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031081679
171 https://doi.org/10.1038/286803a0
172 rdf:type schema:CreativeWork
173 sg:pub.10.1038/371609a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037221662
174 https://doi.org/10.1038/371609a0
175 rdf:type schema:CreativeWork
176 sg:pub.10.1038/44157 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012355245
177 https://doi.org/10.1038/44157
178 rdf:type schema:CreativeWork
179 sg:pub.10.1038/82601 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029988663
180 https://doi.org/10.1038/82601
181 rdf:type schema:CreativeWork
182 sg:pub.10.1038/82609 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053535235
183 https://doi.org/10.1038/82609
184 rdf:type schema:CreativeWork
185 sg:pub.10.1038/nature06718 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012554580
186 https://doi.org/10.1038/nature06718
187 rdf:type schema:CreativeWork
188 sg:pub.10.1038/nature06876 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018542411
189 https://doi.org/10.1038/nature06876
190 rdf:type schema:CreativeWork
191 sg:pub.10.1038/nature08152 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034361762
192 https://doi.org/10.1038/nature08152
193 rdf:type schema:CreativeWork
194 sg:pub.10.1038/ng1178 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019185949
195 https://doi.org/10.1038/ng1178
196 rdf:type schema:CreativeWork
197 sg:pub.10.1038/sj.gt.3302657 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044765773
198 https://doi.org/10.1038/sj.gt.3302657
199 rdf:type schema:CreativeWork
200 https://app.dimensions.ai/details/publication/pub.1081868961 schema:CreativeWork
201 https://app.dimensions.ai/details/publication/pub.1082180968 schema:CreativeWork
202 https://doi.org/10.1002/jez.1402040302 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051817183
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1006/dbio.2001.0346 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001587048
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1016/0012-1606(75)90381-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012233613
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1016/0092-8674(94)90030-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028497067
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1016/j.cell.2004.07.024 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021280382
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1016/j.devcel.2008.01.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031150571
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1016/j.ydbio.2004.02.016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028241851
215 rdf:type schema:CreativeWork
216 https://doi.org/10.1016/j.ydbio.2005.11.037 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021699873
217 rdf:type schema:CreativeWork
218 https://doi.org/10.1016/j.ydbio.2006.05.026 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034988058
219 rdf:type schema:CreativeWork
220 https://doi.org/10.1016/j.ydbio.2007.09.021 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005954097
221 rdf:type schema:CreativeWork
222 https://doi.org/10.1016/s0167-7799(01)01911-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032890492
223 rdf:type schema:CreativeWork
224 https://doi.org/10.1073/pnas.93.6.2348 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008863055
225 rdf:type schema:CreativeWork
226 https://doi.org/10.1093/icb/22.1.131 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059652625
227 rdf:type schema:CreativeWork
228 https://doi.org/10.1126/science.212.4498.993 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062523140
229 rdf:type schema:CreativeWork
230 https://doi.org/10.1126/science.644323 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062637613
231 rdf:type schema:CreativeWork
232 https://doi.org/10.1146/annurev-cellbio-092910-154115 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050815305
233 rdf:type schema:CreativeWork
234 https://doi.org/10.1242/dev.01906 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035425867
235 rdf:type schema:CreativeWork
236 https://doi.org/10.1242/dev.02529 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005841899
237 rdf:type schema:CreativeWork
238 https://doi.org/10.1242/dev.081752 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042389659
239 rdf:type schema:CreativeWork
240 https://doi.org/10.2144/000113238 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069096074
241 rdf:type schema:CreativeWork
242 https://www.grid.ac/institutes/grid.419537.d schema:alternateName Max Planck Institute of Molecular Cell Biology and Genetics
243 schema:name DFG Research Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany
244 Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
245 rdf:type schema:Organization
246 https://www.grid.ac/institutes/grid.5808.5 schema:alternateName University of Porto
247 schema:name DFG Research Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany
248 Graduate Program in Areas of Basic and Applied Biology, Abel Salazar Biomedical Sciences Institute, University of Porto, 4099-003 Porto, Portugal
249 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...