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Loss-of-function mutations in PTCH1 are associated with altered neuronal development and the malignant brain tumour medulloblastoma. As a result of differences between murine and human development, molecular and cellular perturbations that arise from human PTCH1 mutations remain poorly understood. Here, we used cerebellar organoids differentiated from human induced pluripotent stem cells combined with CRISPR\/Cas9 gene editing to investigate the earliest molecular and cellular consequences of PTCH1 mutations on human cerebellar development. Our findings demonstrate that developmental mechanisms in cerebellar organoids reflect in vivo processes of regionalisation and SHH signalling, and offer new insights into early pathophysiological events of medulloblastoma tumorigenesis without the use of animal models.<\/jats:p>","DOI":"10.1242\/dmm.050323","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T08:04:49Z","timestamp":1709021089000},"source":"Crossref","is-referenced-by-count":33,"title":["<i>PTCH1<\/i>\n                    -mutant human cerebellar organoids exhibit altered neural development and recapitulate early medulloblastoma tumorigenesis"],"prefix":"10.1242","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6168-0116","authenticated-orcid":false,"given":"Max J.","family":"van Essen","sequence":"first","affiliation":[{"name":"University of Oxford 1 Nuffield Department of Clinical Neurosciences , , Oxford OX3 9DU , UK"},{"name":"Kavli Institute of Nanoscience Discovery, University of Oxford 2 , Oxford OX1 3QU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5682-0671","authenticated-orcid":false,"given":"Elizabeth J.","family":"Apsley","sequence":"additional","affiliation":[{"name":"University of Oxford 1 Nuffield Department of Clinical Neurosciences , , Oxford OX3 9DU , UK"},{"name":"Kavli Institute of Nanoscience Discovery, University of Oxford 2 , Oxford OX1 3QU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5357-8231","authenticated-orcid":false,"given":"Joey","family":"Riepsaame","sequence":"additional","affiliation":[{"name":"Genome Engineering Oxford, Sir William Dunn School of Pathology, University of Oxford 3 , South Parks Road, OX1 3RE Oxford , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3364-1587","authenticated-orcid":false,"given":"Ruijie","family":"Xu","sequence":"additional","affiliation":[{"name":"St. Jude Children's Research Hospital 4 Department of Developmental Neurobiology , , 262 Danny Thomas Place, Memphis, TN 38105-3678 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1220-5252","authenticated-orcid":false,"given":"Paul A.","family":"Northcott","sequence":"additional","affiliation":[{"name":"St. Jude Children's Research Hospital 4 Department of Developmental Neurobiology , , 262 Danny Thomas Place, Memphis, TN 38105-3678 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0297-6675","authenticated-orcid":false,"given":"Sally A.","family":"Cowley","sequence":"additional","affiliation":[{"name":"James and Lillian Martin Centre for Stem Cell Research, Sir William Dunn School of Pathology, University of Oxford 5 , South Parks Road, OX1 3RE , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7285-3526","authenticated-orcid":false,"given":"John","family":"Jacob","sequence":"additional","affiliation":[{"name":"University of Oxford 1 Nuffield Department of Clinical Neurosciences , , Oxford OX3 9DU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5238-4902","authenticated-orcid":false,"given":"Esther B. 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