Number of oligodendrocyte progenitors recruited to the lesioned spinal cord is modulated by the levels of the cell cycle regulatory protein p27Kip-1.
Remyelination is a critical step for recovery of function after demyelination and defines the ability to generate new myelin. This repair process is dependent on the presence of resident oligodendrocyte progenitors (OLPs) that have been shown to remyelinate axons after demyelination. We have previously shown that the levels of the cell cycle inhibitor p27Kip-1 modulate the number of neonatal cortical OLPs. We now asked whether this cell cycle molecule plays also a role in regulating the number of adult OLP in the spinal cord after demyelination induced by lysolecithin injection. The proliferative response of OLP in the spinal cord of injected wild-type (wt) and p27Kip-1 null mice was evaluated 3 days after lesion. In vivo labeling with bromodeoxyuridine (BrdU) was used to identify cells in S phase. Double immunofluorescence for the OLP marker NG2, and for BrdU was used to count the number of proliferating progenitors. Consistent with a role of p27Kip-1 in regulating the number of adult OLP in the injured spinal cord, a larger number of proliferating OLPs was observed in p27Kip-1null mice compared with wild-type controls. These cells were able to differentiate as assessed by the presence of MBP+ cells in the spinal cord 14 days after injury. We conclude that the cellular levels of the cell cycle inhibitor p27Kip-1 modulate the repair response of OLPs to injury in the adult spinal cord.
Department Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. casaccpa@umdnj.edu
David P
DP
Crockett
Mark
M
Burshteyn
Corina
C
Garcia
Michela
M
Muggironi
Patrizia
P
Casaccia-Bonnefil
D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count; D018797:Cell Cycle Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D008244:Lysophosphatidylcholines; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D016196:S Phase / Q000235:genetics; D013118:Spinal Cord Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D008244:Lysophosphatidylcholines; D004676:Myelin Basic Protein; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D001973:Bromodeoxyuridine