Differential regulation of the zinc finger genes Krox-20 and Krox-24 (Egr-1) suggests antagonistic roles in Schwann cells

Abstract

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.