Epithelial Markers aSMA, Krt14, and Krt19 Unveil Elements of Murine Lacrimal Gland Morphogenesis and Maturation

Abstract

As an element of the lacrimal apparatus, the lacrimal gland (LG) produces the aqueous part of the tear film, which protects the eye surface. Therefore, a defective LG can lead to serious eyesight impairment. Up to now, little is known about LG morphogenesis and subsequent maturation. In this study, we delineated elements of the cellular and molecular events involved in LG formation by using three epithelial markers, namely aSMA, Krt14, and Krt19. While aSMA marked a restricted epithelial population of the terminal end buds (TEBs) in the forming LG, Krt14 was found in the whole embryonic LG epithelial basal cell layer. Interestingly, Krt19 specifically labeled the presumptive ductal domain and subsequently, the luminal cell layer. By combining these markers, the Fucci reporter mouse strain and genetic fate mapping of the Krt14+ population, we demonstrated that LG epithelium expansion is fuelled by a patterned cell proliferation, and to a lesser extent by epithelial reorganization and possible mesenchymal-to-epithelial transition. We pointed out that this epithelial reorganization, which is associated with apoptosis, regulated the lumen formation. Finally, we showed that the inhibition of Notch signaling prevented the ductal identity from setting, and led to a LG covered by ectopic TEBs. Taken together our results bring a deeper understanding on LG morphogenesis, epithelial domain identity, and organ expansion.

Ectodysplasin-A signaling is a key integrator in the lacrimal gland–cornea feedback loop

“…Edar was previously reported in the LG epithelial pre-bud at E14 (Pispa et al, 2003). However, LG branching morphogenesis seemed delayed and did not initiate before E16 in mice from the C57BL/6J background, compared with E15 in ICR mice (Kuony and Michon, 2017) (Fig. S1).…”

“…In our previous work, we showed an increase of epithelial ductal tree complexity and amount of terminal end buds (TEBs) during LG early branching morphogenesis, from E16 to E18 (Kuony and Michon, 2017). Here, we used the same approach to investigate the impact of Eda loss-of-function on LG ductal and acinar compartment formation at E17 and E18 ( Fig.…”

“…After a budding and ductal elongation period starting at embryonic day (E) 14 in mouse, LG branching morphogenesis begins around E16 and continues after birth. Our previous work showed that the LG continues its growth in postnatal stages, reaching its full size by postnatal day (P) 50 (Kuony and Michon, 2017). Numerous signaling pathways are involved in LG morphogenesis, such as fibroblast growth factor (FGF), Notch and Wnt pathways (Chen et al, 2014;Dean et al, 2005;Dvoriantchikova et al, 2017;Makarenkova et al, 2000;Tsau et al, 2011).…”

SPRR2C, DEFB4A, WIF1, CRY2, and KRT19 are correlated with the development of atopic eczema

“…The variable expression of KRT15andKRT19 in oral squamous cell carcinoma (OSCC) and squamous intraepithelial neoplasm (SIN) results in their divergent biological behaviors and roles in pathogenesis, indicating that they may be used as markers to classify OSCC and SIN [33]. KRT19 may also function as a speci c epithelial marker [34]. Expression of KRT19 in the skin may be an additional characterization of skin stem cells under pathological and normal conditions [35].…”

Establishment of long-term serum-free culture for lacrimal gland stem cells aiming at lacrimal gland repair

“…1e) and Epcam (Additional file 5: Figure S2 A), while endothelial cell marker VEGFR2 or fibroblast marker FAP-α could not be detected (Additional file 5: Figure S2 A), suggesting that the spheroid cells were epithelia rather than endothelial cells or fibroblasts. Previous studies indicated that Krt14 is the marker for stem/progenitor cells of secretory glands [11][12][13]. In the adult mouse LG, the basal cells of ducts and myoepithelial cells express keratin (Krt)14, suggesting that these cells might have the characteristics of lacrimal gland stem cells (LGSCs; [14].…”