To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We demonstrate the allotetraploid origin of X. laevis by partitioning its genome into two homeologous subgenomes, marked by distinct families of “fossil” transposable elements. Based on the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged ~34 million years ago (Mya) and combined to form an allotetraploid ~17–18 Mya. 56% of all genes are retained in two homeologous copies. Protein function, gene expression, and the amount of flanking conserved sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.

The planar cell polarity (PCP) signaling system governs many aspects of polarized cell behavior. Here, we use an in vivo model of vertebrate mucociliary epithelial development to show that Dishevelled (Dvl) is essential for the apical positioning of basal bodies. We find that Dvl and Inturned mediate the activation of the Rho GTPase specifically at basal bodies, and that these three proteins together mediate the docking of basal bodies to the apical plasma membrane. Moreover, we find that the docking involves a Dvl-dependent association of basal bodies with membrane-bound vesicles and with the vesicle-trafficking protein, Sec8. Once docked, Dvl and Rho are once again required for the planar polarization of basal bodies that underlies directional beating of cilia. These results demonstrate novel functions for PCP signaling components and suggest that a common signaling appratus governs both apical docking and planar polarization of basal bodies.

Planar Cell Polarity (PCP) is an essential feature of animal tissues, whereby distinct polarity is established within the plane of a cell sheet. Tissue-wide establishment of PCP is driven by multiple global cues, including gradients of gene expression, gradients of secreted Wnt ligands, and anisotropic tissue strain. These cues guide the dynamic, subcellular enrichment of PCP proteins, which can self-assemble into mutually exclusive complexes at opposite sides of a cell. Endocytosis, endosomal trafficking, and degradation dynamics of PCP components further regulate planar tissue patterning. This polarization propagates throughout the whole tissue, providing a polarity axis that governs collective morphogenetic events such as the orientation of subcellular structures and cell rearrangements. Reflecting the necessity of polarized cellular behaviours for proper development and function of diverse organs, defects in PCP have been implicated in human pathologies, most notably in severe birth defects.

Dishevelled proteins are 500 to 600 amino acids in length and are modular. Each contains three highly conserved domains (Box 1, Fig. 2), and whereas the overall structure of Dishevelled has not been defined, structural descriptions of each of the three major domains have been reported (Box 1).The Dishevelled protein regulates many developmental processes in animals ranging from Hydra to humans. Here, we discuss the various known signaling activities of this enigmatic protein and focus on the biological processes that Dishevelled controls. Through its many signaling activities, Dishevelled plays important roles in the embryo and the adult, ranging from cell-fate specification and cell polarity to social behavior. Dishevelled also has important roles in the governance of polarized cell divisions, in the directed migration of individual cells, and in cardiac development and neuronal structure and function. SummaryThe developmental biology of Dishevelled: an enigmatic protein governing cell fate and cell polarity In addition to these commonly discussed domains of Dishevelled, several additional conserved regions deserve attention (Box 1, Fig. 2). For example, there is a basic region and scattered serine/threonine-rich stretches between the DIX and PDZ domains, and there is a proline-rich region with a SH3 protein-binding motif downstream of the PDZ (Penton et al., 2002;Rothbächer et al., 2000). A comparison of Dishevelled protein sequences from hydrazoan to human reveals the presence of several invariant residues downstream of the DEP domain, and the extreme C terminus is very highly conserved across species (Fig. 3). The significance of these conserved Cterminal residues for Dishevelled function remains unexplored. Mechanisms of Dishevelled signalingA fascinating aspect of Dishevelled is that this protein forms a branchpoint that links several widely deployed signaling pathways ( Fig. 1). In this section, we discuss the proteins in the canonical WNT and PCP signaling pathways that function upstream and downstream of Dishevelled. As these signaling cascades have been extensively reviewed elsewhere, we will only attempt a thumbnail sketch of each pathway. Upstream of Dishevelled: WNTs, receptors and coreceptorsWith the sequencing of the human genome, nineteen WNT ligands have been identified (for reviews, see He et al., 2004;Logan and Nusse, 2004). The receptors for the WNT ligand were identified as members of the seven-pass Frizzled (FZ) gene family (see Huang and Klein, 2004). Members of the lowdensity lipoprotein-related receptor proteins (LRP), including Drosophila Arrow and vertebrate LRP5 and LRP6, function as co-receptors for WNTs (Pinson et al., 2000;Tamai et al., 2000;Wehrli et al., 2000). As the LRP co-receptors only impinge on canonical signaling, it is possible that co-receptors may exist that channel WNT signals into the non-canonical arm and several proteins, including NRH1 [p75(NTR)-related transmembrane protein] (Chung et al., 2005;Sasai et al., 2004), protein tyrosine kinase 7 (PTK7) (Lu et al., 2004...

The vertebrate planar cell polarity (PCP) pathway has previously been found to control polarized cell behaviors rather than cell fate. We report here that disruption of Xenopus laevis orthologs of the Drosophila melanogaster PCP effectors inturned (in) or fuzzy (fy) affected not only PCP-dependent convergent extension but also elicited embryonic phenotypes consistent with defective Hedgehog signaling. These defects in Hedgehog signaling resulted from a broad requirement for Inturned and Fuzzy in ciliogenesis. We show that these proteins govern apical actin assembly and thus control the orientation, but not assembly, of ciliary microtubules. Finally, accumulation of Dishevelled and Inturned near the basal apparatus of cilia suggests that these proteins function in a common pathway with core PCP components to regulate ciliogenesis. Together, these data highlight the interrelationships between cell polarity, cellular morphogenesis, signal transduction and cell fate specification.