{"id":"https://openalex.org/W2944749227","doi":"https://doi.org/10.1101/634840","title":"Mesenchymal expression of activated K-ras yields Noonan Syndrome-like bone defects that are rescued by mid-gestational MEK inhibition","display_name":"Mesenchymal expression of activated K-ras yields Noonan Syndrome-like bone defects that are rescued by mid-gestational MEK inhibition","publication_year":2019,"publication_date":"2019-05-10","ids":{"openalex":"https://openalex.org/W2944749227","doi":"https://doi.org/10.1101/634840","mag":"2944749227"},"language":"en","primary_location":{"id":"doi:10.1101/634840","doi":"https://doi.org/10.1101/634840","is_oa":true,"landing_page_url":"https://doi.org/10.1101/634840","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2019/05/10/634840.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2019/05/10/634840.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5043781537","display_name":"Simona Nedelcu","orcid":"https://orcid.org/0000-0001-5473-1368","observed_orcids":["https://orcid.org/0000-0001-5473-1368"]},"institutions":[{"id":"https://openalex.org/I4390039253","display_name":"Koch Institute for Integrative Cancer Research At MIT","ror":"https://ror.org/01xd6q208","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4390039253","https://openalex.org/I63966007"]},{"id":"https://openalex.org/I63966007","display_name":"Massachusetts Institute of Technology","ror":"https://ror.org/042nb2s44","country_code":"US","type":"education","lineage":["https://openalex.org/I63966007"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Simona Nedelcu","raw_affiliation_strings":["Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139","Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139","Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 0139","Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 0239"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139","institution_ids":["https://openalex.org/I63966007"]},{"raw_affiliation_string":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139","institution_ids":["https://openalex.org/I4390039253","https://openalex.org/I63966007"]},{"raw_affiliation_string":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 0139","institution_ids":["https://openalex.org/I63966007"]},{"raw_affiliation_string":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 0239","institution_ids":["https://openalex.org/I63966007"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5057750249","display_name":"Tatsuya Kobayashi","orcid":"https://orcid.org/0000-0003-4264-5117","observed_orcids":["https://orcid.org/0000-0003-4264-5117"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Tatsuya Kobayashi","raw_affiliation_strings":["Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210087915"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045432013","display_name":"Monica Stanciu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4390039253","display_name":"Koch Institute for Integrative Cancer Research At MIT","ror":"https://ror.org/01xd6q208","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4390039253","https://openalex.org/I63966007"]},{"id":"https://openalex.org/I63966007","display_name":"Massachusetts Institute of Technology","ror":"https://ror.org/042nb2s44","country_code":"US","type":"education","lineage":["https://openalex.org/I63966007"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Monica Stanciu","raw_affiliation_strings":["Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139","Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139","Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 0139","Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 0239"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139","institution_ids":["https://openalex.org/I63966007"]},{"raw_affiliation_string":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139","institution_ids":["https://openalex.org/I4390039253","https://openalex.org/I63966007"]},{"raw_affiliation_string":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 0139","institution_ids":["https://openalex.org/I63966007"]},{"raw_affiliation_string":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 0239","institution_ids":["https://openalex.org/I63966007"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066365106","display_name":"Henry M. Kronenberg","orcid":"https://orcid.org/0000-0001-6905-657X","observed_orcids":["https://orcid.org/0000-0001-6905-657X"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Henry M. Kronenberg","raw_affiliation_strings":["Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210087915"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5085454999","display_name":"Jacqueline A. Lees","orcid":"https://orcid.org/0000-0001-9451-2194","observed_orcids":["https://orcid.org/0000-0001-9451-2194"]},"institutions":[{"id":"https://openalex.org/I4390039253","display_name":"Koch Institute for Integrative Cancer Research At MIT","ror":"https://ror.org/01xd6q208","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4390039253","https://openalex.org/I63966007"]},{"id":"https://openalex.org/I63966007","display_name":"Massachusetts Institute of Technology","ror":"https://ror.org/042nb2s44","country_code":"US","type":"education","lineage":["https://openalex.org/I63966007"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jacqueline A. Lees","raw_affiliation_strings":["Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139","Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139","Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 0139","Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 0239"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139","institution_ids":["https://openalex.org/I63966007"]},{"raw_affiliation_string":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139","institution_ids":["https://openalex.org/I4390039253","https://openalex.org/I63966007"]},{"raw_affiliation_string":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 0139","institution_ids":["https://openalex.org/I63966007"]},{"raw_affiliation_string":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 0239","institution_ids":["https://openalex.org/I63966007"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12104","display_name":"Protein Tyrosine Phosphatases","score":0.8300999999046326,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12104","display_name":"Protein Tyrosine Phosphatases","score":0.8300999999046326,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11219","display_name":"Bone Metabolism and Diseases","score":0.05959999933838844,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10169","display_name":"Protein Kinase Regulation and GTPase Signaling","score":0.04019999876618385,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/noonan-syndrome","display_name":"Noonan syndrome","score":1.0},{"id":"https://openalex.org/keywords/kras-g12d","display_name":"KRAS G12D","score":0.9610000252723694},{"id":"https://openalex.org/keywords/mesenchymal-progenitor-cells","display_name":"mesenchymal progenitor cells","score":0.6899999976158142},{"id":"https://openalex.org/keywords/limb-bud","display_name":"limb bud","score":0.8799999952316284},{"id":"https://openalex.org/keywords/hypertrophic-chondrocytes","display_name":"hypertrophic chondrocytes","score":0.9490000009536743},{"id":"https://openalex.org/keywords/mapk-signaling","display_name":"MAPK signaling","score":0.9269999861717224},{"id":"https://openalex.org/keywords/mek-inhibition","display_name":"MEK inhibition","score":0.8939999938011169},{"id":"https://openalex.org/keywords/skeletal-abnormalities","display_name":"skeletal abnormalities","score":0.6019999980926514},{"id":"https://openalex.org/keywords/mouse-model","display_name":"mouse model","score":0.6439999938011169},{"id":"https://openalex.org/keywords/treatment-strategy","display_name":"treatment options","score":0.35199999809265137}],"concepts":[{"id":"https://openalex.org/C198826908","wikidata":"https://www.wikidata.org/wiki/Q1922379","display_name":"Mesenchymal stem cell","level":2,"score":0.606433093547821},{"id":"https://openalex.org/C12387725","wikidata":"https://www.wikidata.org/wiki/Q937024","display_name":"Phenocopy","level":4,"score":0.602925181388855},{"id":"https://openalex.org/C25770073","wikidata":"https://www.wikidata.org/wiki/Q6548937","display_name":"Limb bud","level":3,"score":0.5330537557601929},{"id":"https://openalex.org/C2781403057","wikidata":"https://www.wikidata.org/wiki/Q775480","display_name":"Chondrocyte","level":3,"score":0.5160815119743347},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.471165269613266},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.45195263624191284},{"id":"https://openalex.org/C86370654","wikidata":"https://www.wikidata.org/wiki/Q2277862","display_name":"Limb development","level":3,"score":0.4517372250556946},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.45000436902046204},{"id":"https://openalex.org/C201750760","wikidata":"https://www.wikidata.org/wiki/Q1896218","display_name":"Progenitor cell","level":3,"score":0.4339067339897156},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4117850065231323},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.37937796115875244},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.37129825353622437},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.36014461517333984},{"id":"https://openalex.org/C2780550940","wikidata":"https://www.wikidata.org/wiki/Q502730","display_name":"Cartilage","level":2,"score":0.30523401498794556},{"id":"https://openalex.org/C105702510","wikidata":"https://www.wikidata.org/wiki/Q514","display_name":"Anatomy","level":1,"score":0.26552602648735046},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.23972582817077637},{"id":"https://openalex.org/C196843134","wikidata":"https://www.wikidata.org/wiki/Q33196","display_name":"Embryo","level":2,"score":0.23403221368789673},{"id":"https://openalex.org/C28328180","wikidata":"https://www.wikidata.org/wiki/Q48196","display_name":"Stem cell","level":2,"score":0.1659531593322754},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.15142956376075745},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1101/634840","doi":"https://doi.org/10.1101/634840","is_oa":true,"landing_page_url":"https://doi.org/10.1101/634840","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2019/05/10/634840.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1101/634840","doi":"https://doi.org/10.1101/634840","is_oa":true,"landing_page_url":"https://doi.org/10.1101/634840","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2019/05/10/634840.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9537000060081482}],"study_designs":[],"awards":[{"id":"https://openalex.org/G2360436881","display_name":null,"funder_award_id":"P30-CA14051","funder_id":"https://openalex.org/F4320316943","funder_display_name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology"},{"id":"https://openalex.org/G4766046006","display_name":"Role of miR-17-92 miRNAs in skeletal development and bone homeostasis","funder_award_id":"R01AR056645","funder_id":"https://openalex.org/F4320337362","funder_display_name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases"},{"id":"https://openalex.org/G9000891960","display_name":"Cancer Center Support (Core) Grant","funder_award_id":"P30CA014051","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320316943","display_name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology","ror":"https://ror.org/01xd6q208"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"},{"id":"https://openalex.org/F4320337362","display_name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","ror":"https://ror.org/006zn3t30"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2944749227.pdf","grobid_xml":"https://content.openalex.org/works/W2944749227.grobid-xml"},"referenced_works_count":32,"referenced_works":["https://openalex.org/W1972850991","https://openalex.org/W1973546115","https://openalex.org/W2005508652","https://openalex.org/W2008762441","https://openalex.org/W2010685617","https://openalex.org/W2016596969","https://openalex.org/W2020077729","https://openalex.org/W2023663427","https://openalex.org/W2028436700","https://openalex.org/W2046248667","https://openalex.org/W2048019049","https://openalex.org/W2050389860","https://openalex.org/W2051946560","https://openalex.org/W2058619114","https://openalex.org/W2076627274","https://openalex.org/W2079089760","https://openalex.org/W2082813362","https://openalex.org/W2095885501","https://openalex.org/W2124089267","https://openalex.org/W2127760233","https://openalex.org/W2130607897","https://openalex.org/W2131862834","https://openalex.org/W2136076252","https://openalex.org/W2147888714","https://openalex.org/W2149193631","https://openalex.org/W2150792360","https://openalex.org/W2156070073","https://openalex.org/W2157697960","https://openalex.org/W2160545539","https://openalex.org/W2166692731","https://openalex.org/W4210436031","https://openalex.org/W4212980172"],"related_works":["https://openalex.org/W2015288448","https://openalex.org/W2150792360","https://openalex.org/W1984362145","https://openalex.org/W2147888714","https://openalex.org/W2108100369","https://openalex.org/W2532042160","https://openalex.org/W1994773160","https://openalex.org/W2120419368","https://openalex.org/W2571030736","https://openalex.org/W2140742878"],"abstract_inverted_index":{"ABSTRACT":[0],"Activating":[1],"germline":[2],"K-ras":[3,44,58,110,201],"mutations":[4,277],"cause":[5],"Noonan":[6,249,253,291,347,362],"syndrome":[7,254],"(NS),":[8],"which":[9,56,219,304],"is":[10,118,141,192,255,260,317,341],"characterized":[11,93,261],"by":[12,94,262],"several":[13],"developmental":[14,264,301,339],"deficits":[15],"including":[16,168,266],"cardiac":[17],"defects,":[18],"cognitive":[19],"delays":[20],"and":[21,38,91,151,190,226,230,309],"skeletal":[22,36,244,267,357],"abnormalities.":[23],"NS":[24,35,82],"patients":[25,247,275,360],"have":[26,283],"increased":[27],"signaling":[28,45,222,335],"through":[29],"the":[30,40,67,109,133,136,145,159,172,197,300,320],"MAPK":[31,221],"pathway.":[32],"To":[33],"model":[34,54,287],"defects":[37,131,167,207,245,265,358],"understand":[39],"effect":[41,107],"of":[42,66,81,103,135,158,184,199,296,312,323,333],"hyperactive":[43],"on":[46,108],"normal":[47],"limb":[48,68,233],"development,":[49],"we":[50,163,178,326],"generated":[51,284],"a":[52,95,169,185,213,256,285],"mouse":[53,286],"in":[55,63,97,132,147,171,181,208,216,218,246,303,359],"activated":[57,200],"G12D":[59,111],"was":[60,86,92],"expressed":[61],"specifically":[62],"mesenchymal":[64],"progenitors":[65],"bud.":[69],"These":[70,210,274],"mice":[71],"display":[72,153],"short,":[73],"abnormally":[74],"mineralized":[75],"long":[76,205],"bones":[77],"that":[78,116,180,259,269,278,288,316,328],"phenocopy":[79],"those":[80],"patients.":[83],"This":[84,351],"defect":[85],"first":[87],"apparent":[88],"at":[89],"E14.5,":[90],"delay":[96,146],"bone":[98,113,148,160,206,227,293,305,349],"collar":[99,149,228],"formation.":[100],"Coincident":[101],"mutation":[102],"p53":[104],"had":[105],"no":[106],"induced":[112],"defect,":[114],"arguing":[115],"it":[117],"does":[119],"not":[120],"result":[121],"from":[122],"senescence":[123],"or":[124],"apoptosis.":[125],"Instead,":[126],"our":[127],"data":[128,211],"revealed":[129],"profound":[130],"development":[134],"committed":[137],"osteoblasts;":[138],"their":[139],"appearance":[140],"delayed,":[142],"concordant":[143],"with":[144,248,330,361],"formation,":[150],"they":[152,236],"an":[154,313,331],"aberrant":[155],"localization":[156],"outside":[157],"shaft.":[161],"Additionally,":[162,325],"see":[164],"growth":[165,224,322],"plate":[166,225],"reduction":[170],"hypertrophic":[173],"chondrocyte":[174],"layer.":[175],"Most":[176],"importantly,":[177],"found":[179],"utero":[182],"delivery":[183],"MEK":[186],"inhibitor":[187,332],"between":[188],"E10.5":[189],"E14.5":[191],"sufficient":[193,342],"to":[194,202,271,343],"completely":[195,344],"suppress":[196,345],"ability":[198],"induce":[203],"NS-like":[204,232],"embryogenesis.":[209],"define":[212],"critical":[214,318],"point":[215],"mid-gestation":[217],"elevated":[220],"impairs":[223],"formation":[229,306],"yield":[231],"defects.":[234,294,350],"Moreover,":[235],"offer":[237],"insight":[238],"into":[239],"possible":[240,353],"therapeutic":[241,354],"strategies":[242,355],"for":[243,319,356],"Syndrome.":[250,363],"SIGNIFICANCE":[251],"STATEMENT":[252],"genetic":[257],"condition":[258],"various":[263],"abnormalities":[268],"lead":[270],"short":[272],"stature.":[273],"carry":[276],"activate":[279],"Ras/MAPK":[280,334],"signaling.":[281],"We":[282],"recapitulates":[289],"these":[290,297,346],"Syndrome-like":[292,348],"Analysis":[295],"animals":[298],"establishes":[299],"window":[302,340],"goes":[307],"awry,":[308],"reveals":[310],"disruption":[311],"early":[314],"event":[315],"longitudinal":[321],"bones.":[324],"show":[327],"treatment":[329],"during":[336],"this":[337],"key":[338],"offers":[352]},"counts_by_year":[],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2019-05-16T00:00:00"}