In vivo analysis of Schwann cell programmed cell death in the embryonic chick: regulation by axons and glial growth factor.
The present study uses the embryonic chick to examine in vivo the mechanisms and regulation of Schwann cell programmed cell death (PCD) in spinal and cranial peripheral nerves. Schwann cells are highly dependent on the presence of axons for survival because the in ovo administration of NMDA, which excitotoxically eliminates motoneurons and their axons by necrosis, results in a significant increase in apoptotic Schwann cell death. Additionally, pharmacological and surgical manipulation of axon numbers also affects the relative amounts of Schwann cell PCD. Schwann cells undergoing both normal and induced PCD display an apoptotic-like cell death, using a caspase-dependent pathway. Furthermore, axon elimination results in upregulation of the p75 and platelet-derived growth factor receptors in mature Schwann cells within the degenerating ventral root. During early development, Schwann cells are also dependent on axon-derived mitogens; the loss of axons results in a decrease in Schwann cell proliferation. Axon removal during late embryonic stages, however, elicits an increase in proliferation, as is expected from these more differentiated Schwann cells. In rodents, Schwann cell survival is regulated by glial growth factor (GGF), a member of the neuregulin family of growth factors. GGF administration to chick embryos selectively rescued Schwann cells during both normal PCD and after the loss of axons, whereas other trophic factors tested had no effect on Schwann cell survival. In conclusion, avian Schwann cells exhibit many similarities to mammalian Schwann cells in terms of their dependence on axon-derived signals during early and later stages of development.
Winseck
Adam K
AK
Department of Neurobiology and Anatomy and Neuroscience Program, Wake Forest University, School of Medicine, Winston-Salem, North Carolina 27157, USA.
Caldero
Jordi
J
Ciutat
Dolors
D
Prevette
David
D
Scott
Sheryl A
SA
Wang
Gouying
G
Esquerda
Josep E
JE
Oppenheim
Ronald W
RW
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D061945:Caspase Inhibitors; D002455:Cell Division / Q000502:physiology; D002642:Chick Embryo; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D020890:Neuregulin-1 / Q000378:metabolism*; D020880:Neuregulins / Q000378:metabolism; D009802:Oculomotor Nerve / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D010525:Peripheral Nerves / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D015398:Signal Transduction; D013126:Spinal Nerve Roots / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D015854:Up-Regulation / Q000502:physiology
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D020890:Neuregulin-1; D020880:Neuregulins; D020800:Receptor, Nerve Growth Factor; D016202:N-Methylaspartate; D017479:Receptors, Platelet-Derived Growth Factor