Progressive postnatal motoneuron loss in mice lacking GDF-15.
Growth/differentiation factor-15 (GDF-15) is a widely expressed distant member of the TGF-beta superfamily with prominent neurotrophic effects on midbrain dopaminergic neurons. We show here that GDF-15-deficient mice exhibit progressive postnatal losses of spinal, facial, and trigeminal motoneurons. This deficit reaches a approximately 20% maximum at 6 months and is accompanied by losses of motor axons and significant impairment of rotarod skills. Similarly, sensory neurons in dorsal root ganglia (L4, L5) are reduced by 20%, whereas sympathetic neurons are not affected. GDF-15 is expressed and secreted by Schwann cells, retrogradely transported along adult sciatic nerve axons, and promotes survival of axotomized facial neurons as well as cultured motor, sensory, and sympathetic neurons. Despite striking similarities in the GDF-15 and CNTF knock-out phenotypes, expression levels of CNTF and other neurotrophic factors in the sciatic nerve were unaltered suggesting that GDF-15 is a genuine novel trophic factor for motor and sensory neurons.
Strelau
Jens
J
Neuroanatomy and Interdisciplinary Center for Neurosciences, University of Heidelberg, Heidelberg, Germany.
Strzelczyk
Adam
A
Rusu
Patricia
P
Bendner
Gerald
G
Wiese
Stefan
S
Diella
Francesca
F
Altick
Amy L
AL
von Bartheld
Christopher S
CS
Klein
Rüdiger
R
Sendtner
Michael
M
Unsicker
Klaus
K
D000818:Animals; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism; D005154:Facial Nerve / Q000254:growth & development / Q000503:physiopathology; D005727:Ganglia, Spinal / Q000503:physiopathology; D055436:Growth Differentiation Factor 15 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology*; D009048:Motor Skills / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D012583:Schwann Cells / Q000502:physiology; D012584:Sciatic Nerve / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000502:physiology; D013116:Spinal Cord / Q000254:growth & development / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014276:Trigeminal Nerve / Q000254:growth & development / Q000503:physiopathology
D020934:Ciliary Neurotrophic Factor; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15