title: Ocular surface epithelial and stem cell development.
abstract: Phenotypic features and developmental events involved in the genesis of the limbo-corneal and conjunctival epithelia are described. Together, these two epithelia define the ocular surface. They derive from a small cohort of optic vesicle-induced PAX6+ head ectodermal cells that remain on the surface following lens vesicle formation by the main PAX6+ cell cohort. Both epithelia are stratified, and display wet, non-keratinizing phenotypes. The most significant spatial feature of the limbo-corneal epithelium is the segregation of its supporting stem and early precursor cells to the limbus, the outer vascularized rim separating the cornea from the conjunctiva. These stem cells express ABCG2, a xenobiotic transporter present in stem cells from other organs. ABCG2 transport activity excludes the DNA dye Hoechst 33342, allowing the isolation of the ocular stem cells by flow cytometry, as a unique cohort known as a side 'side population'. Limbal stem cells do not form gap junctions and exist as metabolically isolated entities. Tracking of expression changes in Cx43, the main gap junction protein expressed in both the pre-epithelial ectoderm and in the mature central corneal epithelium, indicates that a limbal stem cell phenotype starts developing very soon after lens vesicle invagination, in advance of the appearance of any recognizable anatomical sub-epithelial limbal feature. Differences in Cx43 expression also reveal the very early nature of the divergence in limbo-corneal and conjunctival lineages. The putative involvement of several early genes, including gradients of PAX6 and differences in expression patterns for members of the Id or msh gene expression regulators are reviewed.
authors.affiliation: Department of Ophthalmology, Mount Sinai School of Medicine, New York 10029, USA. jmario.wolosin@mssm.edu
authors.forename: J Mario
authors.initials: JM
authors.lastname: Wolosin
authors.forename: Murat T
authors.initials: MT
authors.lastname: Budak
authors.forename: M A Murat
authors.initials: MA
authors.lastname: Akinci
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001692:Biological Transport; D003228:Conjunctiva / Q000196:embryology*; D018031:Connexin 43 / Q000378:metabolism; D004475:Ectoderm / Q000378:metabolism; D047108:Embryonic Development; D004847:Epithelial Cells / Q000166:cytology*; D005123:Eye / Q000196:embryology*; D005136:Eye Proteins / Q000378:metabolism; D005434:Flow Cytometry; D017629:Gap Junctions / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D016850:Limbus Corneae / Q000196:embryology*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D012097:Repressor Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001562:Benzimidazoles; D018031:Connexin 43; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; C017807:bisbenzimide ethoxide trihydrochloride