Opposing Wnt Pathways Orient Cell Polarity during Organogenesis

Abstract

Summary The orientation of asymmetric cell division contributes to the organization of cells within a tissue or organ. For example, mirror-image symmetry of the C. elegans vulva is achieved by the opposite division orientation of the vulval precursor cells (VPCs) flanking the axis of symmetry. We characterized the molecular mechanisms contributing to this division pattern. Wnts MOM-2 and LIN-44 are expressed at the axis of symmetry and orient the VPCs towards the center. These Wnts act via Fz/LIN-17 and Ryk/LIN-18, which control β-catenin localization and activate gene transcription. In addition, VPCs on both sides of the axis of symmetry possess a uniform underlying “ground” polarity, established by the instructive activity of Wnt/egl-20. EGL-20 establishes ground polarity via a novel type of signaling involving the Ror receptor tyrosine kinase CAM-1 and the Planar Cell Polarity component Van Gogh/VANG-1. Thus, tissue polarity is determined by the integration of multiple Wnt pathways.

Repression of Wnt signaling by a Fer-type nonreceptor tyrosine kinase

“…No association has previously been made between Wnt signaling and proliferation during embryonic development in C. elegans. However, Wnt signaling has been shown to be required for normal postembryonic divisions in the lateral seam cells (47) and during vulva development (48,49). Our findings establish that hyperactivation of Wnt signaling results in excessive proliferation in the endoderm lineage, which normally undergoes a rigidly fixed number of cell divisions.…”

-Catenin-Dependent Wnt Signaling in C. elegans: Teaching an Old Dog a New Trick

“…In addition to the five receptors mentioned above, the cam-1 gene encodes a Ror tyrosine kinase receptor that functions as a negative Wnt ligand "sink" in several postembryonic processes; only the extracellular cysteine-rich domain is necessary for this activity (Kim and Forrester 2003;Forrester et al 2004;Green et al 2007Green et al , 2008. Recent results, however, suggest it may also function in a positive manner as a Wnt receptor in some processes (Hayashi et al 2009;Kennerdell et al 2009;Song et al 2010;Yamamoto et al 2011).…”

“…elegans has four genes encoding Frizzled receptors, lin-17, mom-5, mig-1, and cfz-2 (Sawa et al 1996;Rocheleau et al 1997;Ruvkun and Hobert 1998;Zhao et al 2003), and a single Ryk/ Derailed receptor homolog encoded by lin-18 (Inoue et al 2004), which appear to function -14, mig-1, vps-35, cam-1(gf), egl-20, lin-17, mig-5, bar-1, pop-1, mab-5 Wild type QR.d QL.d as Wnt receptors. As with the Wnt ligands, for some processes the receptors display genetic redundancy such that Wnt reduction-of-function phenotypes are only seen when multiple genes are mutated (Gleason et al 2006;Pan et al 2006;Green et al 2008;Zinovyeva et al 2008).…”

“…Wnts function in several developmental processes along the anterior-posterior axis during larval development, functioning in cell-fate specification, neuronal migration, and neuronal cell polarity (Eisenmann 2005). For several of these larval Wnt-dependent processes, the Wnt genes also display functional redundancy, such that strong phenotypes are only apparent when multiple Wnt genes are mutated (Zinovyeva and Forrester 2005;Gleason et al 2006;Hilliard and Bargmann 2006;Pan et al 2006;Prasad and Clark 2006;Green et al 2008;Yamamoto et al 2011). This indicates that while in some C. elegans processes, distinct Wnt and Wnt receptor pairings may be used; in other processes, the identity of individual Wnts may not be as important as the reception of a threshold amount of Wnt signal.…”

The Wnt pathway and the roles for its antagonists, DKKS, in angiogenesis

“…Moreover, the Wnt-5a/Ror2 interaction impinges Wnt/b-catenin/ TCF signaling (17,18). Although further detailed studies are required to elucidate their underlying mechanism, some of the Ror actions appear to be mediated through the interaction with several Fz receptors, Dvl, or CK1 (19)(20)(21)(22).…”