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Although null Zfp423 mutants develop cerebellar malformations, the underlying mechanism remains unknown. ZNF423 mutations are associated with Joubert Syndrome, a ciliopathy causing cerebellar vermis hypoplasia and ataxia. ZNF423 participates in the DNA-damage response (DDR), raising questions regarding its role as a regulator of neural progenitor cell cycle progression in cerebellar development. To characterize in vivo the function of ZFP423 in neurogenesis, we analyzed allelic murine mutants in which distinct functional domains are deleted. One deletion impairs mitotic spindle orientation, leading to premature cell cycle exit and Purkinje cell (PC) progenitor pool deletion. The other deletion impairs PC differentiation. In both mutants, cell cycle progression is remarkably delayed and DDR markers are upregulated in cerebellar ventricular zone progenitors. Our in vivo evidence sheds light on the domain-specific roles played by ZFP423 in different aspects of PC progenitor development, and at the same time strengthens the emerging notion that an impaired DDR may be a key factor in the pathogenesis of JS and other ciliopathies.<\/jats:p>","DOI":"10.1242\/dev.155077","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T00:11:01Z","timestamp":1505175061000},"page":"3686-3697","source":"Crossref","is-referenced-by-count":41,"title":["<i>Zfp423\/ZNF423<\/i> regulates cell cycle progression, the mode of cell division and the DNA-damage response in Purkinje neuron progenitors"],"prefix":"10.1242","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-8377","authenticated-orcid":false,"given":"Filippo","family":"Casoni","sequence":"first","affiliation":[{"name":"San 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"},{"name":"Raffaele Scientific Institute 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"},{"name":"Universit\u00e0 Vita-Salute San Raffaele 2 , Milan 20132 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Croci","sequence":"additional","affiliation":[{"name":"San 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"},{"name":"Raffaele Scientific Institute 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Bosone","sequence":"additional","affiliation":[{"name":"San 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"},{"name":"Raffaele Scientific Institute 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"},{"name":"Universit\u00e0 Vita-Salute San Raffaele 2 , Milan 20132 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"D'Ambrosio","sequence":"additional","affiliation":[{"name":"San 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"},{"name":"Raffaele Scientific Institute 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Badaloni","sequence":"additional","affiliation":[{"name":"San 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"},{"name":"Raffaele Scientific Institute 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Gaudesi","sequence":"additional","affiliation":[{"name":"San 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"},{"name":"Raffaele Scientific Institute 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7711-2156","authenticated-orcid":false,"given":"Valeria","family":"Barili","sequence":"additional","affiliation":[{"name":"San 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"},{"name":"Raffaele Scientific Institute 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"},{"name":"Universit\u00e0 Vita-Salute San Raffaele 2 , Milan 20132 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna R.","family":"Sarna","sequence":"additional","affiliation":[{"name":"Cumming School of Medicine, University of Calgary 3 Department of Clinical Neurosciences and Hotchkiss Brain Institute , , Alberta AB T2N 1N4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lino","family":"Tessarollo","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, National Cancer Institute 4 , Frederick, MD 21702-1201 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9462-1040","authenticated-orcid":false,"given":"Ottavio","family":"Cremona","sequence":"additional","affiliation":[{"name":"San 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"},{"name":"Raffaele Scientific Institute 1 Division of Neuroscience , \u2008 , Milan 20132 , Italy"},{"name":"Universit\u00e0 Vita-Salute San Raffaele 2 , Milan 20132 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Hawkes","sequence":"additional","affiliation":[{"name":"Cumming School of Medicine, University of Calgary 5 Department of Cell Biology & Anatomy and Hotchkiss Brain Institute , , Alberta AB T2N 1N4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Warming","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, National Cancer Institute 4 , Frederick, MD 21702-1201 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4594-6273","authenticated-orcid":false,"given":"G. 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