The Id4 HLH protein and the timing of oligodendrocyte differentiation

tin intracellular timer is thought to help control the timing of oligodendr ocyte differentiation. We show here that the expression of the helix-loop-h elix gene Id4 in oligodendrocyte precursor cells decreases irt vivo and in vitro with a time course expected if Id4 is part of the timer. We also show that Id4 expression decreases prematurely when the precursor cells are ind uced to differentiate by mitogen withdrawal, Both Id4 mRNA and protein decr ease together under all of these conditions, suggesting that the control of Id4 expression is transcriptional. Finally, we show that enforced expressi on of Id4 stimulates cell proliferation and blocks differentiation induced by either mitogen withdrawal or treatment with thyroid hormone. These findi ngs suggest that a progressive fall in Id4 transcription is part of the int racellular timer that helps determine when oligodendrocyte precursor cells withdraw from the cell cycle and differentiate.