The Ankyrin Repeat Protein Diego Mediates Frizzled-Dependent Planar Polarization

Abstract

During planar polarization of the Drosophila wing epithelium, the homophilic adhesion molecule Flamingo localizes to proximal/distal cell boundaries in response to Frizzled signaling; perturbing Frizzled signaling alters Flamingo distribution, many cell diameters distant, by a mechanism that is not well understood. This work identifies a tissue polarity gene, diego, that comprises six ankyrin repeats and colocalizes with Flamingo at proximal/distal boundaries. Diego is specifically required for polarized accumulation of Flamingo and drives ectopic clustering of Flamingo when overexpressed. Our data suggest that Frizzled acts through Diego to promote local clustering of Flamingo, and that clustering of Diego and Flamingo in one cell nonautonomously propagates to others.

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…The 'PCP' core components include several transmembrane proteins, such as Frizzled (Fz) (Adler et al, 1997;Vinson and Adler, 1987), Strabismus (Stbm)/Van Gogh (Vang) (Taylor et al, 1998;Wolff and Rubin, 1998), Flamingo (Fmi) (Chae et al, 1999;Usui et al, 1999) and intracellular proteins like Disheveled (Dsh) (Theisen et al, 1994), Prickle (Pk) and Diego (Dgo) (Feiguin et al, 2001). In the Drosophila wing cells, all of those proteins are initially uniformly distributed in the whole cell membrane, however, upon mutual interactions they become asymmetrically segregated; Fz, Dsh and Dgo accumulate at the distal and Stbm/Vang and Pk at the proximal edge of the cell membrane (Axelrod, 2001;Strutt, 2001;Feiguin et al, 2001;Tree et al, 2002;Bastock et al, 2003). The atypical cadherin, Fmi resides on both distal and proximal edges, where it binds neighboring cells through heomophilic interactions (Usui et al, 1999;Shimada et al, 2001).…”

Expression of the ankyrin repeat domain 6 gene (Ankrd6) during mouse brain development

“…AAF58749) with mouse and human genomic sequences, by using the TBLASTN program. Human ANKRD6 was previously identified as an anonymous mRNA (KIAA0957) related to Diego (Feiguin et al, 2001). The mouse and zebrafish mRNA sequences spanning the complete coding region appeared recently as Genbank entries NM_080471 and AY026320 (mouse) and AF395113 (fish).…”

“…This weak similarity region is not present in other mammalian ankyrin repeat containing proteins. The Diego sequence is published by Feiguin et al (2001).…”

“…Recent data suggest that Flamingo interacts with Diego, which encodes an ankyrin repeat domain protein (Feiguin et al, 2001). In mammals, three genes homologous to Flamingo, named Celsr1-3, encode seven-pass transmembrane protocadherins and are expressed during brain development with distinct patterns.…”

“…To assess whether related genes might be involved in brain development in mammals, we and others studied the expression of the three mammalian genes homologous to Flamingo, named Celsr1, 2, and 3, during mouse brain development (Hadjantonakis et al, 1997(Hadjantonakis et al, , 1998Formstone and Little, 2001;Tissir et al, 2002). Recently, the Drosophila gene Diego was shown to interact with Flamingo in the control of planar cell polarity (Feiguin et al, 2001), suggesting that mammalian gene(s) related to Diego may interact with Celsr1-3. In the present work, we report the isolation and developmental expression pattern of the mouse gene that is the most closely related to Diego.…”