Sprouty2 and -4 regulate axon outgrowth by hippocampal neurons.
Sprouty proteins act as negative feedback inhibitors of fibroblast growth factor (FGF) signaling. FGFs belong to the neurotrophic factors and are involved in axonal growth during development and repair. We investigated the expression of Sprouty isoforms in hippocampal neurons as well as the regulation of Sprouty2 and -4 during development and their role in axon growth. Sprouty2 and -4 were located in the nucleus, the cytoplasm, in dendrites, and axons of hippocampal neurons concentrated in growth cones. During development in vivo and differentiation in vitro, expression of Sprouty2 and -4 was gradually downregulated in hippocampal neurons. Between 5 and 24 days in culture expression of both Sprouty isoforms was reduced by 70%. In vivo expression of Sprouty2 was reduced by 79% and of Sprouty4 by 93% on postnatal day 14 compared to embryonic day 16.5. Downregulation of Sprouty2 and -4 by shRNAs strongly promoted elongative axon growth by cultured hippocampal neurons, which was further increased by FGF-2 treatment. In addition, FGF-2 reduced expression of Sprouty2 by 33% and of Sprouty4 by 44%. Together, our results imply that Sprouty2 and -4 are downregulated in the hippocampus during postnatal brain development and that they can act as regulators of developmental axon growth.
Division of Neuroanatomy, Innsbruck Medical University, Muellerstrasse 59, A-6020 Innsbruck, Austria.
Barbara
B
Hausott
Natalie
N
Vallant
Bettina
B
Schlick
Maria
M
Auer
Benedikt
B
Nimmervoll
Gerald J
GJ
Obermair
Christoph
C
Schwarzer
Fangping
F
Dai
Beate
B
Brand-Saberi
Lars
L
Klimaschewski
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors*; D020439:Growth Cones / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C499037:Spry4 protein, mouse; D005346:Fibroblast Growth Factors; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse