Growth/differentiation factor 15 promotes EGFR signalling, and regulates proliferation and migration in the hippocampus of neonatal and young adult mice.
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.
Department of Neurobiology, Interdisciplinary Centre for Neuroscience (IZN), Ruprecht-Karls University of Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
Carmen
C
Carrillo-García
Sebastian
S
Prochnow
Ina K
IK
Simeonova
Jens
J
Strelau
Gabriele
G
Hölzl-Wenig
Claudia
C
Mandl
Klaus
K
Unsicker
Oliver
O
von Bohlen Und Halbach
Francesca
F
Ciccolini
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine; D002232:Carbocyanines; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000378:metabolism*; D005434:Flow Cytometry; D005453:Fluorescence; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
C582073:1,1'-dioleyl-3,3,3',3'-tetramethylindocarbocyanine; C514936:CXCR4 protein, mouse; D002232:Carbocyanines; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D019718:Receptors, CXCR4; D066246:ErbB Receptors; D001616:beta-Galactosidase; D001973:Bromodeoxyuridine
EGFR; GDF15; Hippocampus; Migration; Mouse; Neurogenesis; Proliferation