{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:03:21Z","timestamp":1791857001836,"version":"4.3.4"},"reference-count":59,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T00:00:00Z","timestamp":1620518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002203","name":"Brain Tumour Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002203","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001273","name":"CHILDREN with CANCER UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001273","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012618","name":"National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012618","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We understand little of the pathogenesis of developmental cortical lesions, because we understand little of the diversity of the cell types that contribute to the diseases or how those cells interact. We tested the hypothesis that cellular diversity and cell\u2013cell interactions play an important role in these disorders by investigating the signalling molecules in the commonest cortical malformations that lead to childhood epilepsy, focal cortical dysplasia (FCD) and tuberous sclerosis (TS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptional profiling clustered cases into molecularly distinct groups. Using gene expression data, we identified the secretory signalling molecules in FCD\/TS and characterised the cell types expressing these molecules. We developed a functional model using organotypic cultures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 113 up\u2010regulated secretory molecules in FCDIIB\/TS. The top 12 differentially expressed genes (DEGs) were validated by immunohistochemistry. This highlighted two molecules, Chitinase 3\u2010like protein 1 (CHI3L1) and C\u2010C motif chemokine ligand 2 (CCL2) (MCP1) that were expressed in a unique population of small cells in close proximity to balloon cells (BC). We then characterised these cells and developed a functional model in organotypic slice cultures. We found that the number of CHI3L1 and CCL2 expressing cells decreased following inhibition of mTOR, the main aberrant signalling pathway in TS and FCD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings highlight previously uncharacterised small cell populations in FCD and TS which express specific signalling molecules. These findings indicate a new level of diversity and cellular interactions in cortical malformations and provide a generalisable approach to understanding cell\u2013cell interactions and cellular heterogeneity in developmental neuropathology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12715","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T08:47:25Z","timestamp":1617353245000},"page":"781-795","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Identifying cellular signalling molecules in developmental disorders of the brain: Evidence from focal cortical dysplasia and tuberous sclerosis"],"prefix":"10.1111","volume":"47","author":[{"given":"Yao\u2010Feng","family":"Li","sequence":"first","affiliation":[{"name":"Developmental Biology and Cancer Research &amp; Teaching Department UCL Great Ormond Street Institute of Child Health  London UK"},{"name":"Departments of Histopathology Great Ormond Street Hospital NHS Foundation Trust  London UK"},{"name":"Pathology Department Tri\u2010Service General Hospital &amp; National Defence Medical Centre  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Scerif","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research &amp; Teaching Department UCL Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon R.","family":"Picker","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research &amp; Teaching Department UCL Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Stone","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research &amp; Teaching Department UCL Great Ormond Street Institute of Child Health  London UK"},{"name":"Departments of Histopathology Great Ormond Street Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7888-1723","authenticated-orcid":false,"given":"Jessica C.","family":"Pickles","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research &amp; Teaching Department UCL Great Ormond Street Institute of Child Health  London UK"},{"name":"Departments of Histopathology Great Ormond Street Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale A.","family":"Moulding","sequence":"additional","affiliation":[{"name":"ICH GOS Imaging Facility UCL Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee","family":"Avery","sequence":"additional","affiliation":[{"name":"Departments of Histopathology Great Ormond Street Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Virasami","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research &amp; Teaching Department UCL Great Ormond Street Institute of Child Health  London UK"},{"name":"Departments of Histopathology Great Ormond Street Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy R.","family":"Fairchild","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research &amp; Teaching Department UCL Great Ormond Street Institute of Child Health  London UK"},{"name":"Departments of Histopathology Great Ormond Street Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Tisdall","sequence":"additional","affiliation":[{"name":"Neurosurgery Great Ormond Street Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Harkness","sequence":"additional","affiliation":[{"name":"Neurosurgery Great Ormond Street Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Helen","family":"Cross","sequence":"additional","affiliation":[{"name":"Neurosciences Unit UCL Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Hargrave","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research &amp; Teaching Department UCL Great Ormond Street Institute of Child Health  London UK"},{"name":"Neuro\u2010Oncology Great Ormond Street Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Guillemot","sequence":"additional","affiliation":[{"name":"Neural Stem Cell Biology Laboratory The Francis Crick Institute  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon M.","family":"Paine","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Queens Medical Centre Nottingham University NHS Trust  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shireena A.","family":"Yasin","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research &amp; Teaching Department UCL Great Ormond Street Institute of Child Health  London UK"},{"name":"Departments of Histopathology Great Ormond Street Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7833-2158","authenticated-orcid":false,"given":"Thomas S.","family":"Jacques","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research &amp; Teaching Department UCL Great Ormond Street Institute of Child Health  London UK"},{"name":"Departments of Histopathology Great Ormond Street Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70040-7"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1703784"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12462"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02777.x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.05117.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra055323"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10251"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.11.106"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.030"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12596"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12661"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2127"},{"key":"e_1_2_11_14_1","unstructured":"PickerS.Molecular Characterisation of Focal Cortical Dysplasia and Tuberous Sclerosis. Doctoral thesis UCL (University College London)2014."},{"key":"e_1_2_11_15_1","first-page":"1017","article-title":"Sudan Black B treatment reduces autofluorescence and improves resolution of in situ hybridization specific fluorescent signals of brain sections","volume":"25","author":"Oliveira VC","year":"2010","journal-title":"Histol Histopathol"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(91)90128-M"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.07.012"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.07.086"},{"key":"e_1_2_11_19_1","first-page":"e55359","article-title":"Organotypic hippocampal slice cultures as a model to study neuroprotection and invasiveness of tumor cells","volume":"126","author":"Grabiec U","year":"2017","journal-title":"J Vis Exp"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3162-3"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22768"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.12.030"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0173167"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-017-1604-2"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160806"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12107"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12293"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.12.026"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00087"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052659"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.080045"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0226-4"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0893-7"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2017.10.001"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514561906"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12158"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22905"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-9878-2"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2011.00550.x"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31826eaee7"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2005.00026.x"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2009.00341.x"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02547.x"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14550"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06145-8"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2012.00616.x"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1078-8"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13783"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03033.x"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22312"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12444"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.178"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.06.019"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2394"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-061010-113810"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.036"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-013-0251-0"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14934"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06145-8"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31419-2"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12715","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.12715","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12715","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T12:15:04Z","timestamp":1693311304000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.12715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,9]]},"references-count":59,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1111\/nan.12715"],"URL":"https:\/\/doi.org\/10.1111\/nan.12715","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/NAN.12715\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/NAN.12715\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/NAN.12715\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/NAN.12715\/v1\/review2","asserted-by":"object"}]},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,9]]},"assertion":[{"value":"2020-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}