A cell-intrinsic timer that operates during oligodendrocyte development

Multicellular organisms develop on a predictable schedule that depends on b oth cell-intrinsic timers and sequential cell-cell interactions mediated by extracellular signals. The interplay between intracellular timers and extr acellular signals is well illustrated by the development of oligodendrocyte s, the cells that make the myelin in the vertebrate central nervous system. An intrinsic timing mechanism operates in each oligodendrocyte precursor c ell to limit the length of time the cell divides before terminally differen tiating. This mechanism consists of two components, a timing component, whi ch depends on the mitogen platelet-derived growth factor (PDGF) and measure s elapsed time, and an effector component, which depends on thyroid hormone and stops cell division and initiates differentiation at the appropriate t ime. The cell-cycle inhibitor p27/Kip1 accumulates in the precursor cells a s they proliferate and is part of both components of the timer. It seems li kely that similar timing mechanisms operate in other cell lineages. (C) 200 0 John Wiley & Sons, Inc.