Krox-20 controls SCIP expression, cell cycle exit and susceptibility to apoptosis in developing myelinating Schwann cells

The transcription factors Krox-20 and SCIP each play important roles in the differentiation of Schwann cells, However, the genes encoding these two pr oteins exhibit distinct time courses of expression and yield distinct cellu lar phenotypes upon mutation, SCIP is expressed prior to the initial appear ance of Krox-20, and is transient in both the myelinating and non-myelinati ng Schwann cell lineages; while in contrast, Krox-20 appears similar to 24 hours after SCIP and then only within the myelinating lineage, where its ex pression is stably maintained into adulthood, Similarly, differentiation of SCIP-/- Schwann cells appears to transiently stall at the promyelinating s tage that precedes myelination, whereas Krox-20(-/-) cells are, by morpholo gical criteria, arrested at this stage, These observations led us to examin e SCIP regulation and Schwann cell phenotype in Krox-20 mouse mutants, We f ind that in Krox-20(-/-) Schwann cells, SCIP expression is converted from t ransient to sustained, We further observe that both Schwann cell proliferat ion and apoptosis, which are normal features of SCIP+ cells, are also marke dly increased late in postnatal development in Krox-20 mutants relative to wild type, and that the levels of cell division and apoptosis are balanced to yield a stable number of Schwann cells within peripheral nerves, These d ata demonstrate that the loss of Krox-20 in myelinating Schwann cells arres ts differentiation at the promyelinating stage, as assessed by SCIP express ion, mitotic activity and susceptibility to apoptosis.