Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool

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dc.contributor.author Zega, Ksenija
dc.contributor.author Jovanovic, Vukasin M.
dc.contributor.author Vitic, Zagorka
dc.contributor.author Niedzielska, Magdalena
dc.contributor.author Knaapi, Laura
dc.contributor.author Jukic, Marin M.
dc.contributor.author Partanen, Juha
dc.contributor.author Friedel, Roland F.
dc.contributor.author Lang, Roland
dc.contributor.author Brodski, Claude
dc.date.accessioned 2017-11-24T10:24:01Z
dc.date.available 2017-11-24T10:24:01Z
dc.date.issued 2017-11-09
dc.identifier.citation Zega , K , Jovanovic , V M , Vitic , Z , Niedzielska , M , Knaapi , L , Jukic , M M , Partanen , J , Friedel , R F , Lang , R & Brodski , C 2017 , ' Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool ' , Frontiers in Molecular Neuroscience , vol. 10 , 372 . https://doi.org/10.3389/fnmol.2017.00372
dc.identifier.other PURE: 94150773
dc.identifier.other PURE UUID: 8b792a00-a786-4ddc-8635-7a32e30a0a74
dc.identifier.other WOS: 000414756300001
dc.identifier.other Scopus: 85041626332
dc.identifier.uri http://hdl.handle.net/10138/228754
dc.description.abstract Hydrocephalus can occur in children alone or in combination with other neurodevelopmental disorders that are often associated with brain overgrowth. Despite the severity of these disorders, the molecular and cellular mechanisms underlying these pathologies and their comorbidity are poorly understood. Here, we studied the consequences of genetically inactivating in mice dual-specificity phosphatase 16 (Dusp16), which is known to negatively regulate mitogen-activated protein kinases (MAPKs) and which has never previously been implicated in brain development and disorders. Mouse mutants lacking a functional Dusp16 gene (Dusp16 =) developed fully-penetrant congenital obstructive hydrocephalus together with brain overgrowth. The midbrain aqueduct in Dusp16 = mutants was obstructed during mid-gestation by an expansion of neural progenitors, and during later gestational stages by neurons resulting in a blockage of cerebrospinal fluid (CSF) outflow. In contrast, the roof plate and ependymal cells developed normally. We identified a delayed cell cycle exit of neural progenitors in Dusp16 = mutants as a cause of progenitor overproliferation during midgestation. At later gestational stages, this expanded neural progenitor pool generated an increased number of neurons associated with enlarged brain volume. Taken together, we found that Dusp16 plays a critical role in neurogenesis by balancing neural progenitor cell proliferation and neural differentiation. Moreover our results suggest that a lack of functional Dusp16 could play a central role in the molecular mechanisms linking brain overgrowth and hydrocephalus. en
dc.format.extent 15
dc.language.iso eng
dc.relation.ispartof Frontiers in Molecular Neuroscience
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject DUSP16
dc.subject hydrocephalus
dc.subject brain overgrowth
dc.subject megalencephaly
dc.subject macrocephaly
dc.subject neurogenesis
dc.subject neural differentiation
dc.subject neuronal progenitors
dc.subject CELLS LEADS
dc.subject MOUSE MODEL
dc.subject STEM-CELLS
dc.subject 3112 Neurosciences
dc.subject 3124 Neurology and psychiatry
dc.title Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool en
dc.type Article
dc.contributor.organization Biosciences
dc.contributor.organization Genetics
dc.contributor.organization Developmental neurogenetics
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.3389/fnmol.2017.00372
dc.relation.issn 1662-5099
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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