Growth/differentiation factor 15 promotes EGFR signalling, and regulates proliferation and migration in the hippocampus of neonatal and young adult mice

TY - JOUR

T1 - Growth/differentiation factor 15 promotes EGFR signalling, and regulates proliferation and migration in the hippocampus of neonatal and young adult mice

AU - Carrillo-García, Carmen

AU - Prochnow, Sebastian

AU - Simeonova, Ina K

AU - Strelau, Jens

AU - Hölzl-Wenig, Gabriele

AU - Mandl, Claudia

AU - Unsicker, Klaus

AU - von Bohlen Und Halbach, Oliver

AU - Ciccolini, Francesca

PY - 2014/2/1

Y1 - 2014/2/1

N2 - 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.

AB - 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.

KW - Analysis of Variance

KW - Animals

KW - Animals, Newborn

KW - Bromodeoxyuridine

KW - Carbocyanines

KW - Cell Movement

KW - Cell Proliferation

KW - Flow Cytometry

KW - Fluorescence

KW - Gene Expression Regulation, Developmental

KW - Growth Differentiation Factor 15

KW - Hippocampus

KW - Immunohistochemistry

KW - Mice

KW - Real-Time Polymerase Chain Reaction

KW - Receptor, Epidermal Growth Factor

KW - Receptors, CXCR4

KW - Signal Transduction

KW - beta-Galactosidase

U2 - 10.1242/dev.096131

DO - 10.1242/dev.096131

M3 - SCORING: Journal article

C2 - 24496615

VL - 141

SP - 773

EP - 783

JO - DEVELOPMENT

JF - DEVELOPMENT

SN - 0950-1991

IS - 4

ER -