1. Growth/differentiation factor 15 promotes EGFR signalling, and regulates proliferation and migration in the hippocampus of neonatal and young adult mice
- Author
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Claudia Mandl, Jens Strelau, Sebastian Prochnow, Carmen Carrillo-García, Gabriele Hölzl-Wenig, Oliver von Bohlen und Halbach, Klaus Unsicker, Francesca Ciccolini, and Ina K. Simeonova
- Subjects
Receptors, CXCR4 ,Growth Differentiation Factor 15 ,Mouse ,Cellular differentiation ,EGFR ,Neurogenesis ,Proliferation ,Hippocampal formation ,Real-Time Polymerase Chain Reaction ,Hippocampus ,Fluorescence ,Mice ,Downregulation and upregulation ,Cell Movement ,Animals ,Epidermal growth factor receptor ,CXC chemokine receptors ,Molecular Biology ,Migration ,Cell Proliferation ,Analysis of Variance ,biology ,Dentate gyrus ,Gene Expression Regulation, Developmental ,Carbocyanines ,Flow Cytometry ,beta-Galactosidase ,Stem Cells and Regeneration ,Molecular biology ,Immunohistochemistry ,Cell biology ,ErbB Receptors ,GDF15 ,Animals, Newborn ,Bromodeoxyuridine ,biology.protein ,Developmental Biology ,Signal Transduction - Abstract
The activation of epidermal growth factor receptor (EGFR) affects multiple aspects of neural precursor behaviour, including proliferation and migration. Telencephalic precursors acquire EGF responsiveness and upregulate EGFR expression at late stages of development. The events regulating this process and its significance are still unclear. We here show that in the developing and postnatal hippocampus (HP), growth/differentiation factor (GDF) 15 and EGFR are co-expressed in primitive precursors as well as in more differentiated cells. We also provide evidence that GDF15 promotes responsiveness to EGF and EGFR expression in hippocampal precursors through a mechanism that requires active CXC chemokine receptor (CXCR) 4. Besides EGFR expression, GDF15 ablation also leads to decreased proliferation and migration. In particular, lack of GDF15 impairs both processes in the cornu ammonis (CA) 1 and only proliferation in the dentate gyrus (DG). Importantly, migration and proliferation in the mutant HP were altered only perinatally, when EGFR expression was also affected. These data suggest that GDF15 regulates migration and proliferation by promoting EGFR signalling in the perinatal HP and represent a first description of a functional role for GDF15 in the developing telencephalon.
- Published
- 2014