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The Journal of Neuroscience, June 1, 2002, 22(11):4509-4521

In Vivo Analysis of Schwann Cell Programmed Cell Death in the Embryonic Chick: Regulation by Axons and Glial Growth Factor

Adam K. Winseck1, Jordi Calderó2, Dolors Ciutat2, David Prevette1, Sheryl A. Scott3, Gouying Wang3, Josep E. Esquerda2, and Ronald W. Oppenheim1

1 Department of Neurobiology and Anatomy and Neuroscience Program, Wake Forest University, School of Medicine, Winston-Salem, North Carolina 27157, 2 Unitat de Neurobiologia Cellular, Department de Ciencies Mediques Basiques, Facultat de Medicina, Universitat de Lleide, 25198 Lleida, Catalonia, Spain, and 3 Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah 84132

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.

Key words: Schwann cells; programmed cell death; chick embryo; proliferation; peripheral nerves; neuregulin


Copyright © 2002 Society for Neuroscience  0270-6474/02/22114509-13$05.00/0


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[Abstract] [Full Text] [PDF]



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