Basic helix-loop-helix proteins and the timing of oligodendrocyte differentiation

An intracellular timer in oligodendrocyte precursor cells is thought to hel p control the timing of their differentiation. We show here that the expres sion of the Hes5 and Mash1 genes, which encode neural-specific bHLH protein s, decrease and increase, respectively, in these cells with a time course e xpected if the proteins are part of the timer. We show that enforced expres sion of Hes5 in purified precursor cells strongly inhibits the normal incre ase in the thyroid hormone receptor protein TR beta 1, which is thought to be part of the timing mechanism; it also strongly inhibits the differentiat ion induced by either mitogen withdrawal or thyroid hormone treatment. Enfo rced expression of Mash1, bg contrast, somewhat accelerates the increase in TR beta 1 protein. These findings suggest that Hes5 and Mash1 may be part of the cell-intrinsic timer in the precursor cells.