Show simple item record

dc.creatorZega, K
dc.creatorJovanović, V.M
dc.creatorVitić, Z
dc.creatorNiedzielska, M
dc.creatorKnaapi, L
dc.creatorJukić, Marin
dc.creatorPartanen, J
dc.creatorFriedel, R.H
dc.creatorLang, R
dc.creatorBrodski, C
dc.date.accessioned2019-09-02T12:01:55Z
dc.date.available2019-09-02T12:01:55Z
dc.date.issued2017
dc.identifier.issn1662-5099
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2981
dc.description.abstractHydrocephalus 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 mid-gestation. 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.publisherFrontiers Media S.A.
dc.rightsopenAccess
dc.sourceFrontiers in Molecular Neuroscience
dc.subjectBrain overgrowthen
dc.subjectDUSP16en
dc.subjectHydrocephalusen
dc.subjectMacrocephalyen
dc.subjectMegalencephalyen
dc.subjectNeural differentiationen
dc.subjectNeurogenesisen
dc.subjectNeuronal progenitorsen
dc.titleDusp16 deficiency causes congenital obstructive hydrocephalus and brain overgrowth by expansion of the neural progenitor poolen
dc.typearticle
dc.rights.licenseBY
dcterms.abstractЈовановић, В.М; Витић, З; Јукић, Марин; Ланг, Р; Бродски, Ц; Фриедел, Р.Х; Партанен, Ј; Ниедзиелска, М; Кнаапи, Л; Зега, К;
dc.citation.volume10
dc.citation.other10: -
dc.citation.rankM21
dc.identifier.doi10.3389/fnmol.2017.00372
dc.identifier.scopus2-s2.0-85041626332
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs//bitstream/id/1590/2979.pdf
dc.identifier.rcubconv_4641
dc.type.versionpublishedVersion


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record