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Growth/differentiation factor 15 promotes EGFR signalling, and regulates proliferation and migration in the hippocampus of neonatal and young adult mice
- Source :
- Development (Cambridge, England)
- Publication Year :
- 2014
-
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.
- 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
Subjects
Details
- ISSN :
- 14779129
- Volume :
- 141
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Development (Cambridge, England)
- Accession number :
- edsair.doi.dedup.....7eb8769418040d22bc5a8e4796e440f3