Dyrk1A Influences Neuronal Morphogenesis Through Regulation of Cytoskeletal Dynamics in Mammalian Cortical Neurons
Year: 2012
Type: article
Abstract: Down syndrome (DS) is the most frequent genetic cause of mental retardation. Cognitive dysfunction in these patients is correlated with reduced dendritic branching and complexity, along with fewer spines of abnormal shape that characterize the cortical neuronal profile of DS. DS phenotypes are caused by the disruptive effect of specific trisomic genes. Here, we report that overexpression of dual-specificity tyrosine phosphorylation-regulated kinase 1A, DYRK1A, is sufficient to produce the dendritic alterations observed in DS patients. Engineered changes in Dyrk1A gene dosage in vivo strongly alter the postnatal dendritic arborization processes with a similar progression than in humans. In cultured mammalian cortical neurons, we determined a reduction of neurite outgrowth and synaptogenesis. The mechanism underlying neurite dysgenesia involves changes in the dynamic reorganization of the cytoskeleton.
Source: Cerebral Cortex
Institutions: Universitat Pompeu Fabra, Barcelona Biomedical Research Park, Centre for Biomedical Network Research on Rare Diseases, Centre for Genomic Regulation, Instituto Cajal, Biomedical Research Networking Center on Neurodegenerative Diseases, Centro de Investigación Biomédica en Red, Universidad Politécnica de Madrid, University of Castilla-La Mancha, Centres Científics i Tecnològics de la Universitat de Barcelona, Universitat de Barcelona, Center for Biomedical Research of La Rioja, University of Amsterdam
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: E-Rare, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Ministerio de Ciencia e Innovación, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Fundação para a Ciência e a Tecnologia, Instituto de Salud Carlos III, Departament d'Universitats, Recerca i Societat de la Informació
OpenAlex ID: W2128649861