Sonam S , Srnak JA , Perry KJ , Henry JJ .

R01 EY023979 NEI NIH HHS

             stem cell development

	Fig. 1. Larvae (stage 50–52) and adult (stage 66) Xenopus eyes. (A) Tadpole eye showing regions of the cornea. Region enclosed by white dotted line represents the central cornea (cc), green dotted line represents the region enclosing the peripheral cornea (pc), and the pigmented skin epithelium (sk) lies outside this line. (B) Schematic drawing of the larval Xenopus eye. The corneal epithelium is shaded light yellow, while the skin is shaded light grey. (C) Hoechst labeling in a larval corneal whole-mount. (D) Adult Xenopus eye. White dotted line encloses the central cornea (cc), green dotted line encloses the limbal region (lm), and yellow arrowhead points to the ventral eyelid (ve). The pigmented skin (sk) surrounds the eye. (E) Schematic drawing of the adult frog eye. The corneal epithelium is shaded light yellow, while the eyelid and skin is shaded light grey. (F) Hoechst labeling in a cross-section of adult Xenopus cornea. (a) apical surface of corneal epithelium, (b) basal surface of corneal epithelium, (ce) corneal epithelium, (de) dorsal eyelid, (en) corneal endothelium, (i) inner portion of eyelid, (ln) lens, (o) outer surface of eyelid, (on) optic nerve, (rt) retina, (st) corneal stalk, (sr) stroma, (vc) vitreous chamber. Scale bar in F equals 470 μm for A, 520 μm for C, 800 μm for D, and 400 μm for F. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
	Fig. 2. Confocal and fluorescence light microscopic images showing p63 antibody staining in X. laevis epithelial tissues. (A–D) Larval cornea whole-mounts showing p63 expression (green) is restricted to all basal cells (nuclei) of the central and peripheral cornea, as labeled. (A′-D′) Merged images for A-D with Hoechst labeled nuclei (magenta). (A-A′) Apical cells of central cornea exhibit no p63 expression. (B-B′) Localized p63 labeling is seen in all nuclei of the basal epithelium. (C-C′) p63 is not expressed in apical cells of peripheral corneal epithelium. (D-D′) All nuclei of basal cells in the peripheral cornea have uniform expression for p63. (E–H) Localization of p63 (green) in cryosections of adult cornea, eyelid and skin. The apical surface is located towards the top of each image, and the basal surface towards the bottom. (E′-H′) Merged images for E-H with Hoechst labeled nuclei (magenta). (E-E′) p63 labeling is detected in nuclei of basal and intermediate cells of the central cornea, but not in the nuclei of apical cells. The nuclei in the basal epithelium have relatively higher levels of p63 staining than those in the intermediate layer. (F-F′) In the limbal region, p63 label is primarily detected in nuclei of basal epithelial cells along with moderate expression in intermediate layer cells. (G-G′) Ventral eyelid showing p63 staining is localized to the nuclei of cells present mainly in the outer surface of the eyelid, with the cells in basal layer showing higher staining intensity. Some weak expression maybe seen in scattered basal cells within the inner surface of the eyelid. (H-H′) p63 expression is also detected in the surrounding skin epithelium, with nuclei in the basal layer showing higher expression compared to those of the intermediate layer cells. No staining is detected in cells of the outermost, apical layer of the skin. ive, inner ventral eyelid; ove, outer ventral eyelid. Scale bar in H′ equals 25 μm for A-D, A′-D′, and 50 μm for E-H, E′-H’. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
	Fig. 3. Confocal and fluorescence light microscopic images showing immunofluorescent staining for Paired box protein 6 (Pax6) in larval and adult frog epithelia. (A–D) Pax6 (green) localizes to the basal epithelial cells of central and peripheral cornea in the tadpoles, as labeled. (A′-D′) Merged images for A-D with Hoechst labeled nuclei (magenta). (A-A′) Pax6 expression is undetectable in apical cells of the central cornea. (B-B′) Both the nucleus and cytoplasm of basal cells in the central corneal epithelium show uniform Pax6 staining. However, expression is excluded from the peri-nuclear region in these cells. Pax6-positive cells have a tight packing arrangement. (C-C′) Pax6 is not expressed in the apical cells of peripheral corneal epithelium. (D-D′) Basal cells in the peripheral cornea also express Pax6. Fewer Pax6-positive cells were detected in the peripheral region. (E–H) Cross-sections of adult frog cornea, eyelid and skin stained with Pax6 (green) antibody, as labeled. The apical surface is located towards the top of each image and the basal surface towards the bottom. (E′-H′) Merged images for E-H with Hoechst labeled nuclei (magenta). (E-E′) Pax6 staining is not observed in the central cornea. (F-F′) Pax6 expression is also undetected in the limbal region. (G-G′) Pax6 staining is noted only in apical cells of the outer surface of the ventral eyelid, where expression is primarily localized to the cytoplasm of these cells. (H-H′) A similar pattern of Pax6 expression is seen in apical cells in the skin epithelium, outside the cornea. ive, inner ventral eyelid; ove, outer ventral eyelid. Scale bar in H′ equals 25 μm for A-D, A′-D′, and 50 μm for E-H, E′-H’. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
	Fig. 4. Antibody localization for Transcription factor 7 like 2 (Tcf7l2). Representative images from confocal and fluorescence light microscopy for larval and post-metamorphic frog corneas, as labeled. (A) Whole mount of larval Xenopus cornea showing presence of Tcf7l2 (green) labeled cells in the skin epithelium, surrounding the cornea. Tcf7l2-positive cells are rarely seen in the peripheral cornea. Regions labeled are those shown in B-G and B′-G’. (B–G) Higher magnification confocal images showing the distribution of Tcf7l2 (green) labeled cells in skin and cornea of larval animals, as labeled. (B′-G′) Merged images for B-G with Hoechst labeled nuclei (magenta). (B-B′) Apical cells of the skin epithelium exhibit Tcf7l2 antibody labeling. Tcf7l2 has cytoplasmic expression in a majority of these apical epithelial cells. (C-C′) Skin basal cells do not express Tcf7l2. (D-D′) No expression is observed in the apical cells of the central cornea. (E-E′) Basal cells in the central corneal epithelium also do not show presence of Tcf7l2. (F-F′) The apical epithelium of the peripheral cornea is predominantly devoid of Tcf7l2-positive cells. Tcf7l2 expressing cells (shown by white arrowhead) are rarely detected in the apical layer of the peripheral cornea. (G-G′) Basal epithelial cells of the peripheral cornea are devoid of antibody labeling. (H–K) Immunofluorescent staining for Tcf7l2 (green) on frozen sections of adult frog epithelia, as labeled. The apical surface is located towards the top of each image, and the basal surface towards the bottom. (H′-K′) Merged images for H-K with Hoechst labeled nuclei (magenta). (H-H′) Tcf7l2 staining is not present in the epithelial cell layers of the central cornea. (I-I′) No Tcf7l2 expression is detected in cells of the limbal epithelium. (J-J′) Cells in the basal and intermediate layers of the outer surface of the ventral eyelid show Tcf7l2 staining, with no expression noted in apical cells. The inner surface epithelium of the eyelid is negative for this protein. (K-K′) Tcf7l2 expression is observed in the basal and intermediate cells of the surrounding skin epithelium. Superficial cells of skin epithelium do not label with this antibody. cc, central cornea; ive, inner ventral eyelid; ove, outer ventral eyelid; pc, peripheral cornea; sk, skin. Scale bar in K′ equals 200 μm for A, 25 μm for B-G, B′-G′, and 50 μm for H-K, H′-K’. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
	Fig. 5. Confocal and fluorescence light microscopic images showing cellular localization of Keratin 19 (Krt19) in larval and post-metamorphic frog epithelia. (A–D) Antibody labeling in whole corneas showing the distribution and appearance of Krt19 (green) labeled cells in larval stages, as labeled. (A′-D′) Merged images for A-D with Hoechst labeled nuclei (magenta). (A-A′) Apical cells of the central corneal epithelium exhibit very faint Krt19 labeling. (B-B′) Krt19 is primarily localized in the cytoplasm of cells in the basal epithelium of the central cornea. Krt19 labeling looks uniform throughout the basal layer. (C-C′) Apical epithelium of the peripheral cornea with very weak staining for Krt19. (D-D′) Localized Krt19 labeling in the cytoplasm of all cells in the basal epithelium of the peripheral cornea. (E–H) Krt19 (green) immunostaining in mature Xenopus cornea, eyelid and skin, as labeled. The apical surface is located towards the top of each image and the basal surface towards the bottom. (E′-H′) Merged images for E-H with Hoechst labeled nuclei (magenta). (E-E′) Krt19 is detected in all the epithelial layers of the central cornea. Krt19 predominantly localizes to the apical epithelial cells, where it forms a layer on the surface of the corneal epithelium (indicated by white arrowheads in E and E′). (F-F′) Krt19 localization is observed in all epithelial layers of the limbal area. (G-G′) Ventral eyelid showing Krt19 labeling. Inner surface of the eyelid has Krt19-positive cells in all the layers. The staining is restricted to cells in the basal layer of the outer surface of the eyelid. (H-H′) Skin epithelium showing Krt19 staining. The labeled cells are largely localized to the basal layer, with few positive cells found in the intermediate layers. The outermost layer of skin does not express Krt19. ive, inner ventral eyelid; ove, outer ventral eyelid. Scale bar in H′ equals 25 μm for A-D, A′-D′, and 50 μm for E-H, E′-H’. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
	Fig. 6. Immunolocalization of vimentin in larval and adult frog epithelia and deeper tissues. (A–F) Confocal images showing presence of vimentin (green) expressing cells, which are the keratocytes found below the basal layer of the larval corneal epithelium. (A′-F′) Merged images for A-F with Hoechst labeled nuclei (magenta). (A-A′) No vimentin-positive cells were observed in the apical layer of the central cornea. (B-B′) Basal cells in the central cornea also do not express vimentin. (C-C′) In the central cornea region, vimentin expression is found in keratocytes, which have a dendritic morphology. (D-D′) Apical cells of the peripheral cornea do not show stain with vimentin antibody. (E-E′) No vimentin localization is detected in basal epithelial cells of the peripheral cornea of larvae. (F-F′) Keratocytes of the peripheral cornea also express vimentin. (G–J) Fluorescence light microscopic images showing vimentin (green) labeling in cross-sections of adult Xenopus epithelia, as labeled. The apical surface is located towards the top of each image, and the basal surface towards the bottom. (G′-J′) Merged images for G-J with Hoechst labeled nuclei (magenta). (G-G′) Vimentin expression is detected in the keratocytes that are present in the stromal layer. No staining is noted in central corneal epithelium. (H-H′) Vimentin-positive cells are also present in the stroma underlying the limbal epithelium. (I-I′) The eyelid has vimentin labeled cells in the dermis beneath the epithelial layer. (J-J′) Skin epithelium has moderate expression of vimentin, only in the basal cells. The antibody also labels a much higher number of cells in the dermal layer of the skin. ive, inner ventral eyelid; ove, outer ventral eyelid. Scale bar in J′ equals 25 μm for A-F, A′-F′, and 50 μm for G-J, G′-J’. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
	Fig. 7. Immunolabeling of larval and adult Xenopus epithelia with β1-integrin (β1-itg). (A–D) Confocal images showing that expression of β1-itg (green) is restricted to basal epithelial cells of the tadpole cornea. (A′-D′) Merged images for A-D with Hoechst labeled nuclei (magenta). (A-A′) Apical epithelial cells of the central cornea with no β1-itg label detected. (B-B′) β1-itg staining is predominantly membranous in the basal epithelial cells of the central cornea. Weak cytoplasmic expression is also observed in these cells. (C-C′) β1-itg staining is undetectable in the apical cells of the peripheral cornea. (D-D′) β1-itg stained basal epithelial cells in the peripheral cornea. (E–H) Fluorescence light microscopic images displaying β1-itg (green) antibody labeling on cryosections of adult Xenopus tissues, as labeled. The apical surface is located towards the top of each image, and the basal surface towards the bottom. (H′-K′) Merged images for H-K with Hoechst labeled nuclei (magenta). (E-E′) β1-itg is expressed throughout the entire thickness of the central corneal epithelium. A gradient in expression is observed, with the basal epithelial cells showing the highest expression. (F-F′) Limbal epithelial cells express β1-itg, with the maximum expression present in the basal layer. Moderate expression of β1-itg is seen in stromal cells underneath the corneal epithelium. (G-G′) Ventral eyelid showing β1-itg immunoreactivity. Basal cells in the outer surface of the ventral eyelid have higher expression of β1-itg. (H-H′) Epithelial cells in the skin display β1-itg labeling, with basal cells having the highest expression. ive, inner ventral eyelid; ove, outer ventral eyelid. Scale bar in H′ equals 25 μm for A-D, A′-D′, and 50 μm for E-H, E′-H’. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
	Fig. 8. Larval and adult Xenopus epithelia stained with E-cadherin (E-cad) antibody. (A–D) Confocal images showing uniform distribution of E-cad (green) in the membranes of epithelial cells in a larval Xenopus cornea. (A′-D′) Merged images for A-D with Hoechst labeled nuclei (magenta). (A-A′) E-cad localizes to the membranes in apical cells of the central corneal epithelium. (B-B′) Basal cells of the central corneal epithelium show E-cad expression predominantly associated with the membranes. Weak E-cad expression is also detected in the cytoplasm of the basal cells. (C-C′) Membrane bound E-Cad in apical cells of the peripheral corneal epithelium. (D-D′) E-cad labeling is associated with the membranes of basal epithelial cells of the peripheral cornea. (E–H) Fluorescence light microscopic images showing E-cad (green) staining on frozen sections of adult Xenopus epithelia, as labeled. The apical surface is located towards the top of each image, and the basal surface towards the bottom. (H′-K′) Merged images for H-K with Hoechst labeled nuclei (magenta). (E-E′) Epithelial cells throughout the entire thickness of the central cornea have uniform expression of E-cad in the membrane. (F-F′) E-cad localizes to the membrane of all epithelial cells in the limbal region. (G-G′) E-cad uniformly labels the membranes of epithelial cells in the inner and outer surface of the ventral eyelid. (H-H′) Cross-section of skin epithelium with E-cad membrane associated staining in the basal, intermediate and superficial layers. ive, inner ventral eyelid; ove, outer ventral eyelid. Scale bar in H′ equals 25 μm for A-D, A′-D′, and 50 μm for E-H, E′-H’. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
	Fig. 9. Immunofluorescent localization of β-catenin (β-cat) in larval and adult Xenopus epithelia. (A–D) Confocal images showing restricted localization of β-cat (green) in apical epithelial cells of the larval cornea. (A′-D′) Merged images for A-D with Hoechst labeled nuclei (magenta). (A-A′) β-catenin is associated with the membranes of epithelial cells found in the apical layer of the central cornea. (B-B′) No label is detected in the basal epithelial cells of the central cornea. (C-C′) Apical epithelial cells in the peripheral cornea have membrane-bound expression of β-catenin. (D-D′) Basal epithelial cells show no immunoreactivity with the β-catenin antibody. (E–H) Fluorescence light microscopic images display β-catenin (green) localization in cross-sections of adult frog epithelial tissues, as labeled. The apical surface is located towards the top of each image, and the basal surface towards the bottom. (H′-K′) Merged images for H-K with Hoechst labeled nuclei (magenta). (E-E′) β-catenin is widely expressed throughout the full thickness of the central cornea. Staining is also found in the corneal endothelium (en) and is denoted by white arrowheads in E and E’. (F-F′) Epithelial cells in the limbal region also show positive reactivity to the β-catenin antibody. (G-G′) Epithelial cells lining the inner and outer portion of ventral eyelid uniformly express β-catenin. (H-H′) Skin epithelial cells in all layers have membranous β-catenin expression, similar to that found in the cornea. en, corneal endothelium; ive, inner ventral eyelid; ove, outer ventral eyelid. Scale bar in H′ equals 25 μm for A-D, A′-D′, and 50 μm for E-H, E′-H’. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
	Fig. 10. Cellular localization of the transmembrane receptor, p75 in frog epithelial tissues. Confocal and fluorescence light microscopic images show p75 (green) labeling in larval and mature frog corneas. (A) Representative region of a larval whole-mount cornea showing a few scattered p75 more brightly labeled cells in the peripheral cornea (pc), and a higher number of p75 brightly labeled cells distributed in the skin (sk) outside of the cornea. No p75 brightly labeled cells were observed in the central cornea (cc). Higher magnification confocal images of these regions are shown in B-G. (B–G) Distribution of p75 (green) labeled cells in the skin and the cornea of larval animals. (B′-G′) Merged images for B-G with Hoechst labeled nuclei (magenta). (B-B′) The apical epithelium of the skin has cytoplasmic localization of p75 in a higher number of cells (marked by white arrowheads). (C-C′) Moderate expression of p75 is detected in the peri-nuclear region of basal skin epithelial cells. (D-D′) p75 expression is undetectable in the apical epithelium of the central cornea. (E-E′) Basal cells of the central cornea have peri-nuclear expression of p75. (F-F′) High p75 expression is noted in a few apical epithelial cells of the peripheral cornea (marked by white arrowheads). (G-G′) Basal cells in the peripheral cornea have faint expression of p75 in the peri-nuclear region. (H–K) Immunofluorescent staining for p75 (green) on frozen sections of the adult frog epithelial tissues, as labeled. The apical surface is located towards the top of each image, and the basal surface towards the bottom. (H′-K′) Merged images for H-K with Hoechst labeled nuclei (magenta). (H-H′) p75 is expressed throughout the full thickness of the central corneal epithelium. The localization is membranous, as well as cytoplasmic. (I-I′) Epithelial cells present in all the layers of the limbal region have p75 staining. (J-J′) Ventral eyelid showing p75 localization. The epithelia of both inner and outer surfaces of the ventral eyelid have p75 expression. A few cells more brightly labeled with p75 are also detected (marked by white arrowheads). (K-K′) The skin epithelium has p75 expression in all the cellular layers. cc, central cornea; ive, inner ventral eyelid; ove, outer ventral eyelid; pc, peripheral cornea; sk, skin. Scale bar in K′ equals 60 μm in A, 25 μm for B-G, B′-G′, and 50 μm for H-K, H′-K’. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
	Fig. 11. Larval and adult frog epithelia immunostained with Pax6 and Tcf7l2 antibodies. (A–C) Lower magnification confocal images of larval whole-mount cornea showing Pax6 (red), and Tcf7l2 (green) co-staining. The white dotted line represents the boundary demarcating the cornea and skin. (A) A gradient of Pax6 expression is higher in the central cornea (cc), and is lost progressively towards the peripheral cornea (pc), and skin (sk). (B) Tcf7l2-positive cells are abundant in the skin region. (C) Merged image showing Pax6 and Tcf7l2 expression. (D-G, D′-G′ and D”-G′) Cross-sections of adult frog cornea, eyelid and skin immunolabeled with Pax6 (red) and Tcf7l2 (green). The apical surface is located towards the top of each image, and the basal surface towards the bottom. D′, E′, F′ and G′ are merged images for D, D’; E, E’; F, F′ and G, G′, respectively, with Hoechst labeled nuclei (blue). (D, D′ and D′) No Pax6 or Tcf7l2 expression is detected in the central cornea. (E, E′, and E′) The limbal region has undetectable Pax6 or Tcf7l2. (F, F′ and F′) Ventral eyelid region showing Pax6 and Tcf7l2 expression. The inner surface of the eyelid does not stain for either antibody. Outer surface of the eyelid has Pax6 in the apical cells, and Tcf7l2 mainly in the basal layer of cells. (G, G′ and G′) Skin of the adult frog has Pax6 in apical cells of the epithelium, and Tcf7l2 in the basal and intermediate layers of cells. cc, central cornea; ive, inner ventral eyelid; ove, outer ventral eyelid; pc, peripheral cornea; sk, skin. Scale bar in G′ equals 60 μm for A-C, 50 μm for D-G, D′-G′, D′-G”. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
	Fig. 12. Summary of protein localization detected in the epithelial tissues of larval and adult Xenopus, as indicated. Relative expression levels are represented as undetectable, weak, moderate and high, as shown in the key. ‘#’ denotes few positive cells; ‘a’ denotes expression only in the apical layer; ‘b’ denotes expression only in the basal layer; ‘g’ denotes gradient in expression.

Akiyama, Growth factor and growth factor receptor localization in the hair follicle bulge and associated tissue in human fetus. 1996, Pubmed

Akiyama, Growth factor and growth factor receptor localization in the hair follicle bulge and associated tissue in human fetus. 1996, Pubmed
Arce, Diversity of LEF/TCF action in development and disease. 2006, Pubmed
Bandín, Prepatterning and patterning of the thalamus along embryonic development of Xenopus laevis. 2015, Pubmed , Xenbase
Barbacid, Neurotrophic factors and their receptors. 1995, Pubmed
Barbaro, C/EBPdelta regulates cell cycle and self-renewal of human limbal stem cells. 2007, Pubmed
Barbosa-Sabanero, Lens and retina regeneration: new perspectives from model organisms. 2012, Pubmed
Bardag-Gorce, The Role of E-Cadherin in Maintaining the Barrier Function of Corneal Epithelium after Treatment with Cultured Autologous Oral Mucosa Epithelial Cell Sheet Grafts for Limbal Stem Deficiency. 2016, Pubmed
Bothwell, Keeping track of neurotrophin receptors. 1991, Pubmed
Bragulla, Structure and functions of keratin proteins in simple, stratified, keratinized and cornified epithelia. 2009, Pubmed
Budak, Ocular surface epithelia contain ABCG2-dependent side population cells exhibiting features associated with stem cells. 2005, Pubmed
Burns, Specializations of intercellular junctions are associated with the presence and absence of hair cell regeneration in ears from six vertebrate classes. 2013, Pubmed , Xenbase
Carter, The role of integrins in corneal wound healing. 2009, Pubmed
Castro-Muñozledo, Vimentin as a Marker of Early Differentiating, Highly Motile Corneal Epithelial Cells. 2017, Pubmed
Castro-Muñozledo, Review: corneal epithelial stem cells, their niche and wound healing. 2013, Pubmed
Chen, Characterization of putative stem cell phenotype in human limbal epithelia. 2004, Pubmed
Chen, Abnormal corneal epithelial wound healing in partial-thickness removal of limbal epithelium. 1991, Pubmed
Chen, Evidence for beta 1-integrins on both apical and basal surfaces of Xenopus retinal pigment epithelium. 1997, Pubmed , Xenbase
Chiu, Genome-wide view of TGFβ/Foxh1 regulation of the early mesendoderm program. 2014, Pubmed , Xenbase
Chung, Localization of corneal epithelial stem cells in the developing rat. 1992, Pubmed
Chung, Epithelial regeneration after limbus-to-limbus debridement. Expression of alpha-enolase in stem and transient amplifying cells. 1995, Pubmed
Clevers, Wnt/β-catenin signaling and disease. 2012, Pubmed
Collinson, Clonal analysis of patterns of growth, stem cell activity, and cell movement during the development and maintenance of the murine corneal epithelium. 2002, Pubmed
Collinson, Corneal development, limbal stem cell function, and corneal epithelial cell migration in the Pax6(+/-) mouse. 2004, Pubmed
Costamagna, Adult Stem Cells and Skeletal Muscle Regeneration. 2015, Pubmed
Cotsarelis, Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells. 1989, Pubmed
Das, Vimentin knockdown decreases corneal opacity. 2014, Pubmed
Davanger, Role of the pericorneal papillary structure in renewal of corneal epithelium. 1971, Pubmed
Davies, Stem cell activity in the developing human cornea. 2009, Pubmed
Davis, Overexpression of Pax6 in mouse cornea directly alters corneal epithelial cells: changes in immune function, vascularization, and differentiation. 2011, Pubmed
Davis, Requirement for Pax6 in corneal morphogenesis: a role in adhesion. 2003, Pubmed
Day, Transdifferentiation from cornea to lens in Xenopus laevis depends on BMP signalling and involves upregulation of Wnt signalling. 2011, Pubmed , Xenbase
Delp, Spatiotemporally Regulated Ablation of Klf4 in Adult Mouse Corneal Epithelial Cells Results in Altered Epithelial Cell Identity and Disrupted Homeostasis. 2015, Pubmed
Dent, A whole-mount immunocytochemical analysis of the expression of the intermediate filament protein vimentin in Xenopus. 1989, Pubmed , Xenbase
Dhouailly, The vertebrate corneal epithelium: from early specification to constant renewal. 2014, Pubmed
Di Girolamo, Stem cells of the human cornea. 2011, Pubmed
Di Girolamo, Localization of the low-affinity nerve growth factor receptor p75 in human limbal epithelial cells. 2008, Pubmed
Di Iorio, Limbal stem cell deficiency and ocular phenotype in ectrodactyly-ectodermal dysplasia-clefting syndrome caused by p63 mutations. 2012, Pubmed
Di Iorio, Isoforms of DeltaNp63 and the migration of ocular limbal cells in human corneal regeneration. 2005, Pubmed
Djalilian, Down-regulation of Notch signaling during corneal epithelial proliferation. 2008, Pubmed
Dua, Stem cell differentiation and the effects of deficiency. 2003, Pubmed
Edwards-Faret, Cellular composition and organization of the spinal cord central canal during metamorphosis of the frog Xenopus laevis. 2018, Pubmed , Xenbase
Eghtedari, Keratin 14 Expression in Epithelial Progenitor Cells of the Developing Human Cornea. 2016, Pubmed
Elder, Intermediate filament expression by normal and diseased human corneal epithelium. 1997, Pubmed
FREEMAN, LENS REGENERATION FROM THE CORNEA IN XENOPUS LAEVIS. 1963, Pubmed , Xenbase
Figueira, The phenotype of limbal epithelial stem cells. 2007, Pubmed
Filoni, Lens regeneration in larval Xenopus laevis: experimental analysis of the decline in the regenerative capacity during development. 1997, Pubmed , Xenbase
Fini, Keratocyte and fibroblast phenotypes in the repairing cornea. 1999, Pubmed
Fuchs, Crossroads on cytoskeletal highways. 1999, Pubmed
Fujimura, WNT/β-Catenin Signaling in Vertebrate Eye Development. 2016, Pubmed
Gargioli, The lens-regenerating competence in the outer cornea and epidermis of larval Xenopus laevis is related to pax6 expression. 2008, Pubmed , Xenbase
Glaser, PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. 1994, Pubmed
Goldberg, Limbal palisades of Vogt. 1982, Pubmed
Gonzalez, Limbal stem cells: identity, developmental origin, and therapeutic potential. 2018, Pubmed
Guindolet, Storage of Porcine Cornea in an Innovative Bioreactor. 2017, Pubmed
Gumbiner, Regulation of cadherin adhesive activity. 2000, Pubmed
Hamilton, The lens regenerative competency of limbal vs. central regions of mature Xenopus cornea epithelium. 2016, Pubmed , Xenbase
Hamilton, Lens regeneration from the cornea requires suppression of Wnt/β-catenin signaling. 2016, Pubmed , Xenbase
Hanson, Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly. 1994, Pubmed
Hayashi, Immunohistochemical evidence of the origin of human corneal endothelial cells and keratocytes. 1986, Pubmed
Hayashi, N-Cadherin is expressed by putative stem/progenitor cells and melanocytes in the human limbal epithelial stem cell niche. 2007, Pubmed
Henry, The matured eye of Xenopus laevis tadpoles produces factors that elicit a lens-forming response in embryonic ectoderm. 1995, Pubmed , Xenbase
Henry, Inductive interactions in the spatial and temporal restriction of lens-forming potential in embryonic ectoderm of Xenopus laevis. 1987, Pubmed , Xenbase
Henry, Molecular and cellular aspects of amphibian lens regeneration. 2010, Pubmed , Xenbase
Henry, Characterizing gene expression during lens formation in Xenopus laevis: evaluating the model for embryonic lens induction. 2002, Pubmed , Xenbase
Henry, Methods for Examining Lens Regeneration in Xenopus. 2019, Pubmed , Xenbase
Higa, N-cadherin in the maintenance of human corneal limbal epithelial progenitor cells in vitro. 2009, Pubmed
Hoppler, Wnt signalling: variety at the core. 2007, Pubmed
Hsueh, Age-related expressions of p63 and other keratinocyte stem cell markers in rat cornea. 2004, Pubmed
Hu, The structure and development of Xenopus laevis cornea. 2013, Pubmed , Xenbase
Huang, Polarized Wnt signaling regulates ectodermal cell fate in Xenopus. 2014, Pubmed , Xenbase
Huang, E-cadherin is required for cranial neural crest migration in Xenopus laevis. 2016, Pubmed , Xenbase
Hutson, Expression and function of Xenopus laevis p75(NTR) suggest evolution of developmental regulatory mechanisms. 2001, Pubmed , Xenbase
Ikeda, Aberrant actin cytoskeleton leads to accelerated proliferation of corneal epithelial cells in mice deficient for destrin (actin depolymerizing factor). 2003, Pubmed
Ishizaki, Expression of collagen I, smooth muscle alpha-actin, and vimentin during the healing of alkali-burned and lacerated corneas. 1993, Pubmed
Ivaska, Novel functions of vimentin in cell adhesion, migration, and signaling. 2007, Pubmed
Jester, Corneal keratocytes: in situ and in vitro organization of cytoskeletal contractile proteins. 1994, Pubmed
Jones, Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. 1993, Pubmed
Kalha, Bmi1+ Progenitor Cell Dynamics in Murine Cornea During Homeostasis and Wound Healing. 2018, Pubmed
Kanning, Proteolytic processing of the p75 neurotrophin receptor and two homologs generates C-terminal fragments with signaling capability. 2003, Pubmed , Xenbase
Kasper, Patterns of cytokeratin and vimentin expression in the human eye. 1988, Pubmed
Kasper, Heterogeneity in the immunolocalization of cytokeratin specific monoclonal antibodies in the rat eye: evaluation of unusual epithelial tissue entities. 1991, Pubmed
Kasper, Patterns of cytokeratins and vimentin in guinea pig and mouse eye tissue: evidence for regional variations in intermediate filament expression in limbal epithelium. 1992, Pubmed
Kawakita, Intrastromal invasion by limbal epithelial cells is mediated by epithelial-mesenchymal transition activated by air exposure. 2005, Pubmed
Kenyon, Limbal autograft transplantation for ocular surface disorders. 1989, Pubmed
Kha, A model for investigating developmental eye repair in Xenopus laevis. 2018, Pubmed , Xenbase
Kitazawa, PAX6 regulates human corneal epithelium cell identity. 2017, Pubmed
Koroma, The Pax-6 homeobox gene is expressed throughout the corneal and conjunctival epithelia. 1997, Pubmed
Krieger, Dynamic stem cell heterogeneity. 2015, Pubmed
Ksander, ABCB5 is a limbal stem cell gene required for corneal development and repair. 2014, Pubmed
Lambiase, Nerve growth factor promotes corneal healing: structural, biochemical, and molecular analyses of rat and human corneas. 2000, Pubmed
Lauweryns, The transitional zone between limbus and peripheral cornea. An immunohistochemical study. 1993, Pubmed
Lauweryns, A new epithelial cell type in the human cornea. 1993, Pubmed
Lazarides, Intermediate filaments as mechanical integrators of cellular space. 1980, Pubmed
Lee-Liu, The African clawed frog Xenopus laevis: A model organism to study regeneration of the central nervous system. 2017, Pubmed , Xenbase
Lehrer, Strategies of epithelial repair: modulation of stem cell and transit amplifying cell proliferation. 1998, Pubmed
Li, Identification and isolation of candidate human keratinocyte stem cells based on cell surface phenotype. 1998, Pubmed
Li, Transcription Factor PAX6 (Paired Box 6) Controls Limbal Stem Cell Lineage in Development and Disease. 2015, Pubmed
Li, Expression patterns of focal adhesion associated proteins in the developing retina. 2002, Pubmed , Xenbase
Li, Down-regulation of Pax6 is associated with abnormal differentiation of corneal epithelial cells in severe ocular surface diseases. 2008, Pubmed
Li, Identification for Differential Localization of Putative Corneal Epithelial Stem Cells in Mouse and Human. 2017, Pubmed
Li, Coexistence of quiescent and active adult stem cells in mammals. 2010, Pubmed
Linardi, Expression and localization of epithelial stem cell and differentiation markers in equine skin, eye and hoof. 2015, Pubmed
Liu, Corneal epithelium-specific mouse keratin K12 promoter. 1999, Pubmed
Lu, The β-catenin/Tcf4/survivin signaling maintains a less differentiated phenotype and high proliferative capacity of human corneal epithelial progenitor cells. 2011, Pubmed
Lu, Transcription factor TCF4 maintains the properties of human corneal epithelial stem cells. 2012, Pubmed
Lyngholm, Immunohistochemical markers for corneal stem cells in the early developing human eye. 2008, Pubmed
Lyu, Expression of Wnt and MMP in epithelial cells during corneal wound healing. 2006, Pubmed
Lyu, Wnt-7a up-regulates matrix metalloproteinase-12 expression and promotes cell proliferation in corneal epithelial cells during wound healing. 2005, Pubmed
Majo, Oligopotent stem cells are distributed throughout the mammalian ocular surface. 2008, Pubmed
Mei, Frizzled 7 maintains the undifferentiated state of human limbal stem/progenitor cells. 2014, Pubmed
Mendez, Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. 2010, Pubmed
Menzel-Severing, Transcription factor profiling identifies Sox9 as regulator of proliferation and differentiation in corneal epithelial stem/progenitor cells. 2018, Pubmed
Merjava, The spectrum of cytokeratins expressed in the adult human cornea, limbus and perilimbal conjunctiva. 2011, Pubmed
Mescher, Cells of cutaneous immunity in Xenopus: studies during larval development and limb regeneration. 2007, Pubmed , Xenbase
Michel, Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro: keratin 19 expressing cells are differentially localized in function of anatomic sites, and their number varies with donor age and culture stage. 1996, Pubmed
Michiue, High variability of expression profiles of homeologous genes for Wnt, Hh, Notch, and Hippo signaling pathways in Xenopus laevis. 2017, Pubmed , Xenbase
Mikhailova, Human pluripotent stem cell-derived limbal epithelial stem cells on bioengineered matrices for corneal reconstruction. 2016, Pubmed
Mimeault, Recent progress on tissue-resident adult stem cell biology and their therapeutic implications. 2008, Pubmed
Moore, The corneal epithelial stem cell. 2002, Pubmed
Morita, Evaluation of ABCG2 and p63 expression in canine cornea and cultivated corneal epithelial cells. 2015, Pubmed
Moriyama, Anatomical location and culture of equine corneal epithelial stem cells. 2014, Pubmed
Mort, Stem cells and corneal epithelial maintenance: insights from the mouse and other animal models. 2012, Pubmed
Nakamura, The epidermal growth factor receptor (EGFR): role in corneal wound healing and homeostasis. 2001, Pubmed
Nakamura, Hes1 regulates corneal development and the function of corneal epithelial stem/progenitor cells. 2008, Pubmed
Nakatsu, Wnt/β-catenin signaling regulates proliferation of human cornea epithelial stem/progenitor cells. 2011, Pubmed
Nelson, Convergence of Wnt, beta-catenin, and cadherin pathways. 2004, Pubmed
Nguyen, Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia. 2009, Pubmed
Nishina, PAX6 expression in the developing human eye. 1999, Pubmed
Notara, The porcine limbal epithelial stem cell niche as a new model for the study of transplanted tissue-engineered human limbal epithelial cells. 2011, Pubmed
Nusse, Wnt signaling in disease and in development. 2005, Pubmed
Ouyang, WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis. 2014, Pubmed
Pajoohesh-Ganji, K14 + compound niches are present on the mouse cornea early after birth and expand after debridement wounds. 2016, Pubmed
Pajoohesh-Ganji, Integrins in slow-cycling corneal epithelial cells at the limbus in the mouse. 2006, Pubmed
Pajoohesh-Ganji, Regional distribution of alpha9beta1 integrin within the limbus of the mouse ocular surface. 2004, Pubmed
Parapuram, Integrin β1 is necessary for the maintenance of corneal structural integrity. 2011, Pubmed
Parsa, Association of p63 with proliferative potential in normal and neoplastic human keratinocytes. 1999, Pubmed
Patruno, Morphological description of limbal epithelium: searching for stem cells crypts in the dog, cat, pig, cow, sheep and horse. 2017, Pubmed
Pearton, Transdifferentiation of corneal epithelium into epidermis occurs by means of a multistep process triggered by dermal developmental signals. 2005, Pubmed
Pellegrini, p63 identifies keratinocyte stem cells. 2001, Pubmed
Pellegrini, Cultivation of human keratinocyte stem cells: current and future clinical applications. 1998, Pubmed
Perry, Expression of pluripotency factors in larval epithelia of the frog Xenopus: evidence for the presence of cornea epithelial stem cells. 2013, Pubmed , Xenbase
Pitz, Intermediate-filament expression in ocular tissue. 2002, Pubmed
Priya, Identification of human corneal epithelial stem cells on the basis of high ABCG2 expression combined with a large N/C ratio. 2013, Pubmed
Qi, Nerve growth factor and its receptor TrkA serve as potential markers for human corneal epithelial progenitor cells. 2008, Pubmed
Quan, Tcf7l2 localization of putative stem/progenitor cells in mouse conjunctiva. 2016, Pubmed
Quigley, Specification of ion transport cells in the Xenopus larval skin. 2011, Pubmed , Xenbase
Rama, Limbal stem-cell therapy and long-term corneal regeneration. 2010, Pubmed
Ramaesh, Corneal abnormalities in Pax6+/- small eye mice mimic human aniridia-related keratopathy. 2003, Pubmed
Ring, Wnt/catenin signaling in adult stem cell physiology and disease. 2014, Pubmed
Ritchey, The chicken cornea as a model of wound healing and neuronal re-innervation. 2011, Pubmed
Rungger-Brändle, Retinal patterning by Pax6-dependent cell adhesion molecules. 2010, Pubmed , Xenbase
Schermer, Differentiation-related expression of a major 64K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells. 1986, Pubmed
Schlötzer-Schrehardt, Identification and characterization of limbal stem cells. 2005, Pubmed
Schlötzer-Schrehardt, Characterization of extracellular matrix components in the limbal epithelial stem cell compartment. 2007, Pubmed
Scott, E-cadherin distribution and epithelial basement membrane characteristics of the normal human conjunctiva and cornea. 1997, Pubmed
Secker, Limbal epithelial stem cells of the cornea 2008, Pubmed
Shaham, Pax6: a multi-level regulator of ocular development. 2012, Pubmed
Shalom-Feuerstein, ΔNp63 is an ectodermal gatekeeper of epidermal morphogenesis. 2011, Pubmed
Sidney, Phenotypic Change and Induction of Cytokeratin Expression During In Vitro Culture of Corneal Stromal Cells. 2015, Pubmed
Slack, The Xenopus tadpole: a new model for regeneration research. 2008, Pubmed , Xenbase
Stasiak, Keratin 19: predicted amino acid sequence and broad tissue distribution suggest it evolved from keratinocyte keratins. 1989, Pubmed
Stepp, Integrins in the wounded and unwounded stratified squamous epithelium of the cornea. 1993, Pubmed
Stepp, Corneal integrins and their functions. 2006, Pubmed
SundarRaj, Expression of vimentin by rabbit corneal epithelial cells during wound repair. 1992, Pubmed
Suzuki, Coordinated reassembly of the basement membrane and junctional proteins during corneal epithelial wound healing. 2000, Pubmed
Tam, Genome-wide transcription factor localization and function in stem cells 2008, Pubmed
Tandon, Expanding the genetic toolkit in Xenopus: Approaches and opportunities for human disease modeling. 2017, Pubmed , Xenbase
Thoft, The X, Y, Z hypothesis of corneal epithelial maintenance. 1983, Pubmed
Thomas, Identification of Notch-1 expression in the limbal basal epithelium. 2007, Pubmed
Tiwari, KLF4 Plays an Essential Role in Corneal Epithelial Homeostasis by Promoting Epithelial Cell Fate and Suppressing Epithelial-Mesenchymal Transition. 2017, Pubmed
Tomellini, Role of p75 neurotrophin receptor in stem cell biology: more than just a marker. 2014, Pubmed
Tomimori, Evolutionarily conserved expression pattern and trans-regulating activity of Xenopus p51/p63. 2004, Pubmed , Xenbase
Touhami, The role of NGF signaling in human limbal epithelium expanded by amniotic membrane culture. 2002, Pubmed
Tseng, Seeing the future: using Xenopus to understand eye regeneration. 2017, Pubmed , Xenbase
Ueno, Dependence of corneal stem/progenitor cells on ocular surface innervation. 2012, Pubmed
Umemoto, Rat limbal epithelial side population cells exhibit a distinct expression of stem cell markers that are lacking in side population cells from the central cornea. 2005, Pubmed
Uribe, Immunohistochemistry on cryosections from embryonic and adult zebrafish eyes. 2007, Pubmed
Vorkauf, Adhesion molecules in normal and pathological corneas. An immunohistochemical study using monoclonal antibodies. 1995, Pubmed
Wang, Propagation and phenotypic preservation of rabbit limbal epithelial cells on amniotic membrane. 2003, Pubmed
Watanabe, Human limbal epithelium contains side population cells expressing the ATP-binding cassette transporter ABCG2. 2004, Pubmed
Womble, The left-right asymmetry of liver lobation is generated by Pitx2c-mediated asymmetries in the hepatic diverticulum. 2018, Pubmed , Xenbase
Woo, Nerve growth factor and corneal wound healing in dogs. 2005, Pubmed
Xu, Systematic analysis of E-, N- and P-cadherin expression in mouse eye development. 2002, Pubmed
Yan, The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. 2012, Pubmed
Yang, Pro-BDNF-induced synaptic depression and retraction at developing neuromuscular synapses. 2009, Pubmed , Xenbase
Yang, p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. 1999, Pubmed
Yoshida, Cytokeratin 15 can be used to identify the limbal phenotype in normal and diseased ocular surfaces. 2006, Pubmed
Yoshii, Neural retinal regeneration in the anuran amphibian Xenopus laevis post-metamorphosis: transdifferentiation of retinal pigmented epithelium regenerates the neural retina. 2007, Pubmed , Xenbase
You, Neurotrophic factors in the human cornea. 2000, Pubmed
Zelenka, Coordinating cell proliferation and migration in the lens and cornea. 2008, Pubmed
Zhang, Wnt/β-catenin signaling modulates corneal epithelium stratification via inhibition of Bmp4 during mouse development. 2015, Pubmed
Zhang, Basonuclin-null mutation impairs homeostasis and wound repair in mouse corneal epithelium. 2007, Pubmed
Zhao, Adult corneal limbal epithelium: a model for studying neural potential of non-neural stem cells/progenitors. 2002, Pubmed
Zhou, The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. 2001, Pubmed
Zhu, NF2/Merlin is required for the axial pattern formation in the Xenopus laevis embryo. 2015, Pubmed , Xenbase
Zhu, Expression of cell adhesion molecules on limbal and neovascular endothelium in corneal inflammatory neovascularization. 1999, Pubmed
Zieske, Alpha-enolase is restricted to basal cells of stratified squamous epithelium. 1992, Pubmed
Zieske, Regional variation in distribution of EGF receptor in developing and adult corneal epithelium. 1993, Pubmed
van Es, A critical role for the Wnt effector Tcf4 in adult intestinal homeostatic self-renewal. 2012, Pubmed