A role for Wnt/planar cell polarity signaling during lens fiber cell differentiation?

Abstract

Wnt signaling through frizzled (Fz) receptors plays key roles in just about every developmental system that has been studied. Several Wnt-Fz signaling pathways have been identified including the Wnt/planar cell polarity (PCP) pathway. PCP signaling is crucial for many developmental processes that require major cytoskeletal rearrangements. Downstream of Fz, PCP signaling is thought to involve the GTPases, Rho, Rac and Cdc42 and regulation of the JNK cascade. Here we report on the localization of these GTPases and JNK in the lens and assess their involvement in the cytoskeletal reorganization that is a key element of FGF-induced lens fiber cell differentiation.

Ureteric Morphogenesis Requires Fgfr1 and Fgfr2/Frs2α Signaling in the Metanephric Mesenchyme

“…In lens explants, Fgf-induced fiber cell differentiation appears to be driven in part by alterations in expression of planar cell polarity signaling molecules. 35 Perhaps in a similar manner, Fgf signaling could be required to regulate these planar cell polarity molecules in the developing kidney. Alternatively, a recent paper described that in developing lung airway, increases in Erk activity led to alterations in mitotic spindle orientation; 36 thus, the alterations in Erk activation in Fgfr1…”

Genetic and epigenetic mechanisms of gene regulation during lens development

“…In mammals, 19 secreted glycoproteins of the Wnt family bind to any of 10 types of Frizzled (Fz) receptors which have seven transmembrane domains and require the structurally less complex co-receptors LRP5/6 for their function. Wnt signaling functions through three pathways: Wnt/β-catenin ("canonical"), Wnt/planar cell polarity (PCP) and Wnt/Ca 2+ pathways (see (Cadigan and Liu, 2006;Chen et al, 2006). Activation of Frizzled receptors leads to the phosphorylation of Dishevelled (Dsh) proteins and their binding to the intracellular membrane.…”

“…Expression of genes that function in Wnt/β-catenin signaling suggest a role for this pathway in crystallin gene regulation (Lyu and Joo, 2004). In contrast, the Wnt/PCP pathway may play roles in the cytoskeletal rearrangements involved in fiber cell elongation (see Chen et al, 2006).…”

The pulling, pushing and fusing of lens fibers

“…46 Finally, Wnt/PCP signaling via activation of Rho GTPases has been suggested to control lens morphogenesis, fiber cell migration and differentiation. 26 Importantly, given how the activity of the Rho GTPases is regulated by external cues and various effector proteins, a detailed understanding of the regulation of Rho GTPase signaling is necessary for a better appreciation of their role in lens morphogenesis, fiber cell elongation and differentiation, and tensional homeostasis. Further mechanistic studies are critical to unravel the specific role(s) of Rho GTPases and other cytoskeletal regulatory mechanisms involved in regulating the formation and disassembly of fiber cell basal and apical membrane complexes, fiber cell lateral membrane remodeling, and fiber cell-cell adhesive interactions during lens differentiation.…”

“…10,19,21 Similarly, adhesion regulating signaling molecules including integrins, focal adhesion kinase, Cdk5, abl kinase interacting protein (Abi-2), and Rho GTPases have been shown to localize to the fiber cell apical and basal tips. 20,[23][24][25][26] Moreover, isolation and characterization of the fiber cell basal membrane complexes (BMCs) had revealed a symmetric organization of N-cadherin, myosin II, actin in association with myosin light chain kinase, focal adhesion kinase, β1 integrin and caldesmon. 12 The signaling activity, tensional property and dynamics of BMCs are thought to control the coordinated migration of fiber cells along the lens capsule, formation of lens suture line, and lens accommodation.…”