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

Zega K, Jovanovic VM, Vitic Z, Niedzielska M, Knaapi L, Jukic MM, Partanen J, Friedel RF, Lang R, Brodski C (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Frontiers in Molecular Neuroscience Frontiers Research Foundation / Frontiers Media

Book Volume: 10

DOI: 10.3389/fnmol.2017.00372

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 functionalDusp16gene (Dusp16-/-) developed fully-penetrant congenital obstructive hydrocephalus together with brain overgrowth. The midbrain aqueduct inDusp16-/-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 inDusp16-/-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 thatDusp16plays a critical role in neurogenesis by balancing neural progenitor cell proliferation and neural differentiation. Moreover our results suggest that a lack of functionalDusp16could play a central role in the molecular mechanisms linking brain overgrowth and hydrocephalus.

Authors with CRIS profile

Roland Lang Professur für Angeborene Immunität und Pathogenerkennung

Involved external institutions

Ben-Gurion University of the Negev (BGU) / אוניברסיטת בן-גוריון בנגב IL Israel (IL) Icahn School of Medicine at Mount Sinai US United States (USA) (US) Helsingin yliopisto / University of Helsinki FI Finland (FI)

How to cite

APA:

Zega, K., Jovanovic, V.M., Vitic, Z., Niedzielska, M., Knaapi, L., Jukic, M.M.,... Brodski, C. (2017). Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool. Frontiers in Molecular Neuroscience, 10. https://doi.org/10.3389/fnmol.2017.00372

MLA:

Zega, Ksenija, et al. "Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool." Frontiers in Molecular Neuroscience 10 (2017).

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