The airway epithelium forms a protective barrier between the lungs' clean milieu and the outside environment. Several mechanisms, that include proper ion transport, mucus secretion and the expression of junctional proteins, such as connexins (Cx), are involved in ensuring its function. Being the first line of contact with inhaled hostilities, this tissue is in constant threat of injury and has to repair and re-differentiate continuously. The repair process has been widely studied. However, the mechanisms regulating it, which might be deregulated in Cystic Fibrosis (CF), are poorly understood. Here, we investigated mechanisms involved in re-differentiation in injured non-CF and CF epithelia, and whether these intersect with the expression of Cxs at different times of wound repair. Our study shows defects in the differentiating signals in CF and that these signals intersect with Cx expression during repair. We suggest that these mechanisms are synchronized to ensure the re-differentiation of repairing cells.