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
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