Wnt signaling is required for organization of the lens fiber cell cytoskeleton and development of lens three-dimensional architecture.
How an organ develops its characteristic shape is a major issue. This is particularly critical for the eye lens as its function depends on having appropriately ordered three-dimensional cellular architecture. Recent in vitro studies indicate that Wnt signaling plays key roles in regulating morphological events in FGF-induced fiber cell differentiation in the mammalian lens. To further investigate this the Wnt signaling antagonist, secreted frizzled-related protein 2 (Sfrp2), was overexpressed in lens fiber cells of transgenic mice. In these mice fiber cell elongation was attenuated and individual fibers exhibited irregular shapes and consequently did not align or pack regularly; microtubules, microfilaments and intermediate filaments were clearly disordered in these fibers. Furthermore, a striking feature of transgenic lenses was that fibers did not develop the convex curvature typically seen in normal lenses. This appears to be related to a lack of protrusive processes that are required for directed migratory activity at their apical and basal tips as well as for the formation of interlocking processes along their lateral margins. Components of the Wnt/Planar Cell Polarity (PCP) pathway were downregulated or inhibited. Taken together this supports a role for Wnt/PCP signaling in orchestrating the complex organization and dynamics of the fiber cell cytoskeleton.
Chen
Yongjuan
Y
Save Sight Institute, The University of Sydney, NSW 2001, Sydney, Australia.
Stump
Richard J W
RJ
Lovicu
Frank J
FJ
Shimono
Akihiko
A
McAvoy
John W
JW
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism*; D007908:Lens, Crystalline / Q000166:cytology / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology*; D000094742:Secreted Frizzled-Related Proteins
D008565:Membrane Proteins; D051153:Wnt Proteins; C491628:Sfrp2 protein, mouse; D000094742:Secreted Frizzled-Related Proteins