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Neuronal LRP4 regulates synapse formation in the developing CNS

Karakatsani, Andromachi and Marichal, Nicolás and Urban, Severino and Kalamakis, Georgios and Ghanem, Alexander and Schick, Anna and Zhang, Yina and Conzelmann, Karl-Klaus and Rüegg, Markus A. and Berninger, Benedikt and Ruiz de Almodovar, Carmen and Gascón, Sergio and Kröger, Stephan. (2017) Neuronal LRP4 regulates synapse formation in the developing CNS. Development, 144 (24). pp. 4604-4615.

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Abstract

The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reduction in density of synapses and number of primary dendrites. Accordingly, overexpression of LRP4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased number of spines. Transsynaptic tracing mediated by rabies virus revealed a reduced number of neurons presynaptic to the cortical neurons in which LRP4 was knocked down. Moreover, neuron-specific knockdown of LRP4 by in utero electroporation of LRP4 miRNA in vivo also resulted in neurons with fewer primary dendrites and a lower density of spines in the developing cortex and hippocampus. Collectively, our results demonstrate an essential and novel role of neuronal LRP4 in dendritic development and synaptogenesis in the CNS.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Schwede)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Company of Biologists
ISSN:0950-1991
e-ISSN:1477-9129
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:28 May 2018 15:38
Deposited On:28 May 2018 15:34

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