Basic helix-loop-helix proteins and the timing of oligodendrocyte differentiation.
An intracellular timer in oligodendrocyte precursor cells is thought to help control the timing of their differentiation. We show here that the expression of the Hes5 and Mash1 genes, which encode neural-specific bHLH proteins, decrease and increase, respectively, in these cells with a time course expected if the proteins are part of the timer. We show that enforced expression of Hes5 in purified precursor cells strongly inhibits the normal increase in the thyroid hormone receptor protein TR(&bgr;)1, which is thought to be part of the timing mechanism; it also strongly inhibits the differentiation induced by either mitogen withdrawal or thyroid hormone treatment. Enforced expression of Mash1, by 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.
Kondo
T
T
Medical Research Council Developmental Neurobiology Programme, MRC Laboratory for Molecular Cell Biology and the Biology Department, University College London, London, WC1E 6BT, UK. t.kondo@ucl.ac.uk
Raff
M
M
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D010982:Platelet-Derived Growth Factor; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D013963:Thyroid Hormones; D014157:Transcription Factors; C499318:Ascl1 protein, rat; C489686:Hes5 protein, rat; C077478:HES5 protein, human