title: Interactions between lens epithelial and fiber cells reveal an intrinsic self-assembly mechanism.
abstract: How tissues and organs develop and maintain their characteristic three-dimensional cellular architecture is often a poorly understood part of their developmental program; yet, as is clearly the case for the eye lens, precise regulation of these features can be critical for function. During lens morphogenesis cells become organized into a polarized, spheroidal structure with a monolayer of epithelial cells overlying the apical tips of elongated fiber cells. Epithelial cells proliferate and progeny that shift below the lens equator differentiate into new fibers that are progressively added to the fiber mass. It is now known that FGF induces epithelial to fiber differentiation; however, it is not fully understood how these two forms of cells assemble into their characteristic polarized arrangement. Here we show that in FGF-treated epithelial explants, elongating fibers become polarized/oriented towards islands of epithelial cells and mimic their polarized arrangement in vivo. Epithelial explants secrete Wnt5 into the culture medium and we show that Wnt5 can promote directed behavior of lens cells. We also show that these explants replicate aspects of the Notch/Jagged signaling activity that has been shown to regulate proliferation of epithelial cells in vivo. Thus, our in vitro study identifies a novel mechanism, intrinsic to the two forms of lens cells, that facilitates self-assembly into the polarized arrangement characteristic of the lens in vivo. In this way the lens, with its relatively simple cellular composition, serves as a useful model to highlight the importance of such intrinsic self-assembly mechanisms in tissue developmental and regenerative processes.
authors.affiliation: Save Sight Institute, University of Sydney, Australia.
authors.forename: L J
authors.initials: LJ
authors.lastname: Dawes
authors.affiliation: Save Sight Institute, University of Sydney, Australia.
authors.forename: Y
authors.initials: Y
authors.lastname: Sugiyama
authors.affiliation: Discipline of Anatomy and Histology, Bosch Institute, University of Sydney, Australia.
authors.forename: F J
authors.initials: FJ
authors.lastname: Lovicu
authors.affiliation: Save Sight Institute, University of Sydney, Australia.
authors.forename: C G
authors.initials: CG
authors.lastname: Harris
authors.affiliation: Save Sight Institute, University of Sydney, Australia.
authors.forename: E J
authors.initials: EJ
authors.lastname: Shelley
authors.affiliation: Save Sight Institute, University of Sydney, Australia. Electronic address: john.mcavoy@sydney.edu.au.
authors.forename: J W
authors.initials: JW
authors.lastname: McAvoy
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D007908:Lens, Crystalline / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051880:Receptors, Notch / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D000071818:Wnt-5a Protein
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C491837:Wnt5a protein, rat; D005346:Fibroblast Growth Factors
keywords: Development and regeneration; FGF; Jagged; Lens epithelial cells; Lens fiber cells; Notch; Planar cell polarity; Wnt