{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:53:43Z","timestamp":1779378823630,"version":"3.53.1"},"reference-count":44,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015872","name":"University of Lille","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015872","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CNRS"},{"DOI":"10.13039\/501100001677","name":"Inserm","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CHU Lille"},{"name":"Comit\u00e9 de l\u2019Oise de la Ligue Contre le Cancer"},{"name":"Canc\u00e9rop\u00f4le Nord-Ouest"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), plays a critical role in neural development by regulating gene expression through the trimethylation of lysine 27 on histone H3 (H3K27me3), which promotes chromatin remodeling and transcriptional repression. Although PRC2 is known to regulate cell fate specification and gliogenesis, its in vivo functions during vertebrate neurodevelopment, particularly at the level of neuronal subtype differentiation, remain incompletely understood. Here, we investigated the consequences of ezh2 loss-of-function during zebrafish brain development, focusing on oligodendrocyte differentiation, cerebellar neurogenesis, and the formation of neurotransmitter-specific neuronal populations. Using whole-mount in situ hybridization, we found that ezh2 inactivation does not alter the expression of oligodendrocyte lineage markers, indicating that early oligodendrocyte precursor cell specification and myelination are preserved. However, a significant reduction in cerebellar proliferation was observed in ezh2-deficient larvae, as evidenced by the downregulation of pcna and cyclin A2, while other brain regions remained unaffected. Notably, the expression of atoh1c, a key marker of glutamatergic cerebellar progenitors, was strongly reduced at 5 days post fertilization, suggesting a selective role for ezh2 in maintaining cerebellar progenitor identity. This was associated with impaired differentiation of both glutamatergic granule cells and GABAergic Purkinje cells in specific cerebellar subregions. In contrast, the expression of markers for other major neurotransmitter systems remained unaffected, indicating a region-specific requirement for ezh2 in neuronal development. Finally, behavioral analysis revealed a hyperlocomotor phenotype in ezh2\u2212\/\u2212 larvae, consistent with cerebellar dysfunction. Together, these findings identify ezh2 as a key regulator of progenitor maintenance and neuronal differentiation in the cerebellum, highlighting its crucial role in establishing functional cerebellar circuits.<\/jats:p>","DOI":"10.3390\/ijms26199736","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T10:48:07Z","timestamp":1759834087000},"page":"9736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ezh2 Loss-of-Function Alters Zebrafish Cerebellum Development"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7187-3615","authenticated-orcid":false,"given":"Mariette","family":"Hanot","sequence":"first","affiliation":[{"name":"Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277\u2013CANTHER\u2013Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8582-1550","authenticated-orcid":false,"given":"Pamela","family":"V\u00f6lkel","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277\u2013CANTHER\u2013Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6790-6358","authenticated-orcid":false,"given":"Xuefen","family":"Le Bourhis","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277\u2013CANTHER\u2013Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5182-2069","authenticated-orcid":false,"given":"Chann","family":"Lagadec","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277\u2013CANTHER\u2013Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9509-4796","authenticated-orcid":false,"given":"Pierre-Olivier","family":"Angrand","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277\u2013CANTHER\u2013Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.stemcr.2017.05.007","article-title":"MiR-203 Interplays with Polycomb Repressive Complexes to Regulate the Proliferation of Neural Stem\/Progenitor Cells","volume":"9","author":"Liu","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nrg3413","article-title":"From neural development to cognition: Unexpected roles for chromatin","volume":"14","author":"Ronan","year":"2013","journal-title":"Nat. Rev. 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