GSK‐3β and α‐catenin binding regions of β‐catenin exert opposing effects on the terminal ventral optic axonal projection

Abstract

We overexpressed two deletion mutants of the N-terminal domain of ␤-catenin in ventral optic axons in living Xenopus tadpoles. One deletion mutant contained both the ␣-catenin and the GSK-3␤ binding sites of the N-terminal domain of ␤-catenin (NTERM), and the second deletion mutant contained only the GSK-3␤ binding site (␤-cat107). Expression of NTERM in ventral optic axons dispersed and induced anterior and lateral shifts in their targeting locations in the dorsal tectum. In contrast, ␤-cat107 compressed and shifted the synaptic targeting locations of ventral optic axons medially and posteriorly. In addition, NTERMexpressing ventral optic axons formed arbors that were wider than controls whereas ␤-cat107 axonal arbors were narrower compared with controls. These data suggest that the interactions of ␤-catenin with ␣-catenin and GSK-3␤ exert opposing effects on the terminal projections of ventral optic axons. Developmental

A novel mechanism for the transcriptional regulation of Wnt signaling in development

“…4D). Retinal disruption of the repressor complex through loss-of-function mutation of Apc or Gsk3b has previously been shown to result in Wnt signaling derepression and aberrantly patterned axonal projections from the eye to the brain (Wiley et al 2008;Paridaen et al 2009) that are similar to the Wnt derepression (Fig. 4D) and axon projection phenotypes seen in Vax2 À/À mutants (Barbieri et al 1999;Mui et al 2002).…”

“…Cells expressing dnTcf7l2 are therefore ''blind'' to Wnt signaling. Conversely, losing the activity of a single critical component of the Wnt repression machinery-e.g., Apc or Gsk3b-leads to derepression of Wnt signaling even in the absence of a Wnt ligand (Wiley et al 2008;Paridaen et al 2009). …”

“…At the same time, when canonical Wnt signaling is repressed in the developing eye, expression of the dorsal markers is lost and expression of Vax2 expands dorsally (Veien et al 2008;Zhou et al 2008;Fujimura et al 2009). Perturbation of Wnt signaling in the eye has also been shown to result in aberrant axonal projections to the brain that resemble those seen in Vax2 À/À mice (Barbieri et al 1999;Mui et al 2002;Veien et al 2008;Wiley et al 2008;Zhou et al 2008;Paridaen et al 2009). …”

Morphometrics in Developmental Neurobiology: Quantitative Analysis of Growth Cone Motility in Vivo

“…Microtubule and actin interactions also occur in the T zone and C domain of the growth cone, where actin arcs in the T zone exert compressive forces on microtubules in the C domain, facilitating microtubule bundling and aiding in axon navigation (Figure 1; [5]). Previous and current studies from our laboratory show that molecules downstream of Cadherin and Wnt signaling ligands such as β-catenin and APC, that regulate the actin and microtubule cytoskeleton, modulate optic axon growth cone morphology and motility in the optic tract as well as targeting and branching in the optic tectum [6,7]. More generally, it is now clear that the actin and microtubule cytoskeleton of the two growth cone regions are dynamically related, and may influence each other via signaling molecules such as APC [8].…”

Visualizing Morphogenesis with the Processing Programming Language

“…Another study measured and modeled the mean branching angle of axon arbors in vitro (Shefi et al, 2005). Studies showed that molecular perturbations can misshape optic axonal arbors by altering the rates of addition, retraction and lifetime of arbor branches (Wiley et al, 2008;Elul et al, 2003). Some of these molecular perturbations of the optic axonal arbor dynamics have also been associated with disruptions of visual synaptic function (Mannitt et al, 2009;Ruthazer et al, 2006;Alsina et al, 2001).…”