Regeneration of the dermal skeleton and wound epidermis formation depend on BMP signaling in the caudal fin of platyfish.

Fin regeneration has been extensively studied in zebrafish, a genetic model organism. Little is known about regulators of this process in distant fish taxa, such as the Poeciliidae family, represented by the platyfish. Here, we used this species to investigate the plasticity of ray branching morphogenesis following either straight amputation or excision of ray triplets. This approach revealed that ray branching can be conditionally shifted to a more distal position, suggesting non-autonomous regulation of bone patterning. To gain molecular insights into regeneration of fin-specific dermal skeleton elements, actinotrichia and lepidotrichia, we localized expression of the actinodin genes and bmp2 in the regenerative outgrowth. Blocking of the BMP type-I receptor suppressed phospho-Smad1/5 immunoreactivity, and impaired fin regeneration after blastema formation. The resulting phenotype was characterized by the absence of bone and actinotrichia restoration. In addition, the wound epidermis displayed extensive thickening. This malformation was associated with expanded Tp63 expression from the basal epithelium towards more superficial layers, suggesting abnormal tissue differentiation. Our data add to the increasing evidence for the integrative role of BMP signaling in epidermal and skeletal tissue formation during fin regeneration. This expands our understanding of common mechanisms guiding appendage restoration in diverse clades of teleosts.

Upregulation of FOXA2 in uterine luminal epithelium and vaginal basal epithelium of epiERα-/- (Esr1fl/flWnt7aCre/+) mice†.

Forkhead box protein A2 (FOXA2) is a pioneer transcription factor important for epithelial budding and morphogenesis in different organs. It has been used as a specific marker for uterine glandular epithelial cells (GE). FOXA2 has close interactions with estrogen receptor α (ERα). ERα binding to Foxa2 gene in the uterus indicates its regulation of Foxa2. The intimate interactions between ERα and FOXA2 and their essential roles in early pregnancy led us to investigate the expression of FOXA2 in the female reproductive tract of pre-implantation epiERα-/- (Esr1fl/flWnt7aCre/+) mice, in which ERα is conditionally deleted in the epithelium of reproductive tract. In the oviduct, FOXA2 is detected in the ciliated epithelial cells of ampulla but absent in the isthmus of day 3.5 post-coitum (D3.5) Esr1fl/fl control and epiERα-/- mice. In the uterus, FOXA2 expression in the GE appears to be comparable between Esr1fl/fl and epiERα-/- mice. However, FOXA2 is upregulated in the D0.5 and D3.5 but not PND25-28 epiERα-/- uterine luminal epithelial cells (LE). In the vagina, FOXA2 expression is low in the basal layer and increases toward the superficial layer of the D3.5 Esr1fl/fl vaginal epithelium, but FOXA2 is detected in the basal, intermediate, and superficial layers, with the strongest FOXA2 expression in the intermediate layers of the D3.5 epiERα-/- vaginal epithelium. This study demonstrates that loss of ERα in LE and vaginal basal layer upregulates FOXA2 expression in these epithelial cells during early pregnancy. The mechanisms for epithelial cell-type specific regulation of FOXA2 by ERα remain to be elucidated.

The effects of the systemic isotretinoin treatment on ocular surface and meibomian glands: a prospective longitudinal study.

PURPOSE: To assess the effects of systemic isotretinoin therapy (SIT) on the ocular surface, meibomian glands (MG) and cornea microstructure in acne vulgaris (AV) patients. METHODS: Patients with AV (n = 20) and healthy controls (n = 20) were enrolled in the study. All participants underwent ocular surface tests in the order of ocular surface disease index (OSDI) questionnaire, corneal sensitivity, tear break-up time (BUT), fluorescein and lissamine green (LG) staining and Schirmer II test with anaesthesia. MG alterations were evaluated with meibography for upper (UE) and lower eyelids (LE) separately. Corneal basal epithelium and subbasal nerve plexus (SNP) were evaluated using In Vivo Confocal Microscopy (IVCM). RESULTS: Schirmer II test with anaesthesia, BUT, corneal sensitivity, fluorescein and LG staining grades and OSDI score results showed no difference between the control group and the baseline of the patient group. Whereas the meibomian gland dysfunction (MGD) grades, UE and LE meiboscores were higher in the patient group at the baseline (p = 0.013, p = 0.004, p = 0.008 respectively). The Control group possessed higher numbers of total and long nerve fibres compared with patients at the baseline (p ≤ 0.001 for both two values). Compared to the baseline and the third month, BUT decreased and fluorescein staining grades increased (p = 0.017 and p = 0.043, respectively). MGD grades, UE and LE meiboscores increased in the third month compared to the baseline (p < 0.001, p < 0.001, p = 0.008 respectively). Basal epithelial cell density (BECD) decreased in the third month of SIT (p = 0.043). CONCLUSIONS: This prospective study showed that systemic Isotretinoin treatment effects not only ocular surface parameters but also corneal and Meibomian glands structure. Considering early alterations in the course of treatment, ophthalmological assessment and follow-up during SIT are mandatory.

Ocular surface alterations and in vivo confocal microscopic characteristics of corneas in patients with myasthenia gravis.

PURPOSE: To evaluate ocular surface alterations and characteristics of corneal basal epithelium and subbasal nerves in patients with myasthenia gravis. MATERIALS AND METHODS: Myasthenia gravis patients (n = 21) and healthy controls (n = 20) were enrolled. All participants underwent ocular surface testing in the following order: tear break-up time, lissamine green staining, Schirmer I test with anesthesia, and Ocular Surface Disease Index questionnaire. The Cochet-Bonnet esthesiometer was used to measure corneal sensitivity. Basal epithelial cells and subbasal nerves were evaluated using in vivo confocal microscopy. RESULTS: Myasthenia gravis patients had higher Ocular Surface Disease Index score (13.9 ± 15.0 vs 1.4 ± 2.2, p < 0.001) and lissamine green staining score (0.6 ± 0.4 vs 0.2 ± 0.4, p = 0.007). Break-up time score (9.3 ± 3.0 vs 9.9 ± 1.9, p = 0.481) and Schirmer I test score (16.5 ± 9.2 vs 19.3 ± 8.4, p = 0.323) did not differ significantly. Corneal sensation was 0.4 g/mm2 in all eyes. Patients with myasthenia gravis had lower basal epithelial cell density (3775.7 ± 938.1 vs 4983.1 ± 608.5, p < 0.001) and total nerve density (1956.1 ± 373.3 vs 2277.9 ± 405.0, p = 0.012) and higher subbasal nerve tortuosity (1.9 ± 0.8 vs 1.6 ± 0.7, p = 0.007) than controls. A significant increase in Ocular Surface Disease Index scores was found with decreasing basal epithelial cell density (rho = -0.518, p = 0.001). There was a significantly moderate negative correlation between the duration of myasthenia gravis and the number of corneal nerves (rho = -0.497, p = 0.022). CONCLUSION: Significant alterations of basal epithelial cells and subbasal nerves were demonstrated in myasthenia gravis patients although there was no difference of corneal sensitivity between myasthenia gravis patients and healthy controls. Thus, it should be borne in mind that myasthenia gravis patients deserve further evaluation with regard to ocular surface disease.