A developmentally regulated switch directs regenerative growth of Schwann cells through cyclin D1.
Sciatic nerve axons in cyclin D1 knockout mice develop normally, become properly ensheathed by Schwann cells, and appear to function normally. However, in the Wallerian degeneration model of nerve injury, the mitotic response of Schwann cells is completely inhibited. The mitotic block is Schwann cell autonomous and developmentally regulated. Rescue analysis (by "knockin" of cyclin E) indicates that D1 protein, rather than regulatory elements of the D1 gene, provides the essential Schwann cell function. Genetic inhibition of the Schwann cell cycle shows that neuronal responses to nerve injury are surprisingly independent of Schwann cell mitotic responses. Even axonal regrowth into the distal zone of a nerve crush injury is not markedly impaired in cyclin D1-/- mice.
Kim
H A
HA
Department of Cancer Biology, Dana-Farber Cancer Institute, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Pomeroy
S L
SL
Whoriskey
W
W
Pawlitzky
I
I
Benowitz
L I
LI
Sicinski
P
P
Stiles
C D
CD
Roberts
T M
TM
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D019938:Cyclin D1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019927:Cyclin E / Q000235:genetics / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D005812:Genes, Switch / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D008938:Mitosis; D009416:Nerve Regeneration / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D012016:Reference Values; D012583:Schwann Cells / Q000473:pathology / Q000502:physiology*; D014855:Wallerian Degeneration / Q000473:pathology
D019927:Cyclin E; D019938:Cyclin D1