TST-1 OCT-6/SCIP REGULATES A UNIQUE STEP IN PERIPHERAL MYELINATION AND IS REQUIRED FOR NORMAL RESPIRATION/

The terminal differentiation of myelinating glia involves complex inte ractions that culminate in the formation of myelin. The POU domain tra nscription factor Tst-1/Oct-6/SCIP is expressed transiently during mye lination, and we report here that it has a critical role in this devel opmental process. Deletion of the Tst-1/Oct-6/SCIP gene produces a sev ere defect in peripheral myelination by arresting Schwann cell maturat ion before axonal wrapping. Unexpectedly, the activation of major myel in-specific genes appears to be unaffected by the Tst-1/Oct-6/SCIP mut ation, demonstrating that multiple, independently regulated events are required for terminal differentiation of Schwann cells. In addition, aberrant differentiation and migration of specific neurons in Tst-1/Oc t-6/SCIP mutant homozygotes is associated with a fatal breathing defec t, providing a model for investigating the regulation of pulmonary hom eostasis.