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Differential regulation of the zinc finger genesKrox-20 andKrox-24 (Egr-1) suggests antagonistic roles in Schwann cells

1997; Wiley; Volume: 50; Issue: 5 Linguagem: Inglês

10.1002/(sici)1097-4547(19971201)50

1097-4547

Piotr Topilko, Giovanni Levi, Giorgio R. Merlo, Stefano Mantero, Carole Desmarquet, Gianluigi Mancardi, Patrick Charnay,

Genetics and Neurodevelopmental Disorders

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. J. Neurosci. Res. 50:702–712, 1997. © 1997 Wiley-Liss, Inc.