The expression and/or role of Runx proteins in development and regeneration of major ocular glands, lacrimal gland (LG) and meibomian gland (MG), has not been previously studied. LG is an exocrine-type gland that accounts for the bulk of the aqueous portion of the preocular tear film.
24 Murine LG development starts at approximately E13.5 as an invagination of conjunctival epithelium into the surrounding mesenchyme. Subsequently, epithelial ducts form an elaborate network through a process known as branching morphogenesis.
25,26 The branching pattern and function of the LG is regulated by epidermal growth factor, FGFs, bone morphogenetic proteins (BMPs), Wnts, and numerous transcription factors.
27–32 Recent studies indicate that, similar to other exocrine glands (pancreas, salivary, mammary),
33–36 the LG has a high regenerative potential and is able to repair itself even after substantial damage.
37 During LG regeneration, the epithelial component of the gland undergoes epithelial-mesenchymal transition.
24,38 In this process, epithelial cells lose cell junctions, polarity, and epithelial-specific markers, and acquire migratory phenotype and expression of mesenchymal markers.
37 When gland remodeling is completed, cells return to an epithelial phenotype and form new LG ductal and acinar structures.
37 There is also evidence for a population of proliferating nestin-positive stem cells that expand during LG regeneration; a subset of these cells bear markers of myoepithelial cells, suggesting a common progenitor for myoepithelial and epithelial lineages.
37 It is possible that LG regeneration involves both dedifferentiation of mature epithelial cells, and activation, proliferation, and migration of epithelial stem cells.