Differential regulation of the zinc finger genes Krox-20 and Krox-24 (Egr-1) suggests antagonistic roles in Schwann cells.
Krox-20 and Krox-24 (Egr-1) encode closely related zinc finger transcription factors, which interact with the same DNA target sequences. Krox-20 is required for myelination in the peripheral nervous system. Using lacZ knock-in mutant mouse lines as well as immunohistochemical analyses, we have studied the expression of Krox-20 and Krox-24 in the Schwann cell lineage during normal development and following nerve lesion in the mouse and in human neuropathies. During embryogenesis, the two genes are expressed in a successive and mutually exclusive manner, Krox-24 being restricted to Schwann cell precursors and Krox-20 to mature Schwann cells. At birth, Krox-24 is reactivated and the two genes are coexpressed. In the adult, Krox-20 is expressed in myelinating cells, while Krox-24 is restricted to nonmyelinating cells. Following nerve lesion, Krox-24 is strongly induced in Schwann cells, reinforcing the link between its expression and the nonmyelinating and/or proliferative state, whereas Krox-20 is downregulated. These data are consistent with Krox-20 and Krox-24 playing antagonistic roles during the development of the Schwann cell lineage. In particular, their balance of expression might participate in the choice between myelinating and nonmyelinating pathways.
Topilko
P
P
Unité 368 de l'Institut National de la Santé et de la Recherche Médicale, Ecole Normale Supérieure, Paris, France.
Levi
G
G
Merlo
G
G
Mantero
S
S
Desmarquet
C
C
Mancardi
G
G
Charnay
P
P
D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017874:Immediate-Early Proteins; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism; D009422:Nervous System Diseases / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000196:embryology / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D013497:Sural Nerve / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; C497326:EGR2 protein, human; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C486109:Egr1 protein, mouse; C497327:Egr2 protein, mouse; D017874:Immediate-Early Proteins; D014157:Transcription Factors