1. The neural EGF family member CALEB/NGC mediates dendritic tree and spine complexity
- Author
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Robert Nitsch, Nicola Brandt, Burkhard Hassel, Elena E. Pohl, Jan Baumgart, Kristin Franke, Mladen-Roko Rasin, Sergey Khrulev, Johannes Vogt, Nenad Sestan, and Stefan Schumacher
- Subjects
Dendritic spine ,Dendritic Spines ,Morphogenesis ,Hippocampus ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Phosphatidylinositol 3-Kinases ,Animals ,Pseudopodia ,Rats, Wistar ,Molecular Biology ,Cells, Cultured ,Protein Kinase C ,PI3K/AKT/mTOR pathway ,Protein kinase C ,Epidermal Growth Factor ,General Immunology and Microbiology ,TOR Serine-Threonine Kinases ,General Neuroscience ,Membrane Proteins ,Dendrites ,Embryo, Mammalian ,Rats ,Cell biology ,Oncogene Protein v-akt ,Female ,Proteoglycans ,Signal transduction ,Protein Kinases ,Filopodia ,Signal Transduction - Abstract
The development of dendritic arborizations and spines is essential for neuronal information processing, and abnormal dendritic structures and/or alterations in spine morphology are consistent features of neurons in patients with mental retardation. We identify the neural EGF family member CALEB/NGC as a critical mediator of dendritic tree complexity and spine formation. Overexpression of CALEB/NGC enhances dendritic branching and increases the complexity of dendritic spines and filopodia. Genetic and functional inactivation of CALEB/NGC impairs dendritic arborization and spine formation. Genetic manipulations of individual neurons in an otherwise unaffected microenvironment in the intact mouse cortex by in utero electroporation confirm these results. The EGF-like domain of CALEB/NGC drives both dendritic branching and spine morphogenesis. The phosphatidylinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway and protein kinase C (PKC) are important for CALEB/NGC-induced stimulation of dendritic branching. In contrast, CALEB/NGC-induced spine morphogenesis is independent of PI3K but depends on PKC. Thus, our findings reveal a novel switch of specificity in signaling leading to neuronal process differentiation in consecutive developmental events.
- Published
- 2007