Multiple Wnt Signaling Pathways Converge to Orient the Mitotic Spindle in Early C. elegans Embryos

Abstract

How cells integrate the input of multiple polarizing signals during division is poorly understood. We demonstrate that two distinct Caenorhabditis elegans Wnt pathways contribute to the polarization of the ABar blastomere by differentially regulating its duplicated centrosomes. Contact with the C blastomere orients the ABar spindle through a nontranscriptional Wnt spindle alignment pathway, while a Wnt/beta-catenin pathway controls the timing of ABar spindle rotation. The three C. elegans Dishevelled homologs contribute to these processes in different ways, suggesting that functional distinctions may exist among them. We also find that CKI (KIN-19) plays a role not only in the Wnt/beta-catenin pathway, but also in the Wnt spindle orientation pathway as well. Based on these findings, we establish a model for the coordination of cell-cell interactions and distinct Wnt signaling pathways that ensures the robust timing and orientation of spindle rotation during a developmentally regulated cell division event.

Divide and differentiate

“…The Wnt-and Srcsignaling pathways function together to specify both endoderm and EMS division orientation; however, genetic studies suggest that cell fate specification and division orientation can be uncoupled. [31][32][33][34][35] WRM-1, 1 of 4 worm homologs of β-catenin, plays a central role in transducing the P2-EMS signal. 36 WRM-1 exhibits a dynamic localization pattern during EMS mitosis, where signaling drives both cortical and nuclear WRM-1 asymmetries in EMS and its daughters.…”

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

“…Forward and reverse genetic screens identified components of Wnt, MAPK, and Src signaling pathways as being required for endoderm formation (Lin et al 1995;Kaletta et al 1997;Rocheleau et al 1997Rocheleau et al , 1999Meneghini et al 1999;Peters et al 1999;Schlesinger et al 1999;Shin et al 1999;Bei et al 2002;Thorpe and Moon 2004;Walston et al 2004;Huang et al 2007;Phillips et al 2007). Wnt pathway components functioning in endoderm induction include MOM-1/Porcupine, MOM-2/Wnt, MIG-14/ Wntless (a.k.a.…”

“…The Wnt/b-catenin asymmetry (WBA) pathway was the first Wnt pathway characterized in C. elegans (Rocheleau et al 1997;Thorpe et al 1997), and it is known to regulate many asymmetric cell divisions during C. elegans embryonic and larval development ( For some cells whose fate is regulated by the WBA pathway, Frizzled and Disheveled proteins have been found to asymmetrically localize at the cortex of the mother cell on the side at which the Wnt signal is received, whereas negative regulators APC and Axin localize to the opposite side of the mother cell cortex (Park et al 2004;Walston et al 2004;Takeshita and Sawa 2005;Goldstein et al 2006;Mizumoto and Sawa 2007a). Then, upon cell division and the asymmetrical distribution of these cytoplasmic components, Wnt pathway activation occurs in only one of the two daughter cells.…”

“…The worm genome encodes three Disheveled family members, MIG-5, DSH-1, and DSH-2, which function positively in Wnt signaling and which display genetic redundancy in several cases (Ruvkun and Hobert 1998;Walston et al 2004;Eisenmann 2005;King et al 2009). …”

The adhesion GPCR latrophilin – a novel signaling cascade in oriented cell division and anterior-posterior polarity

“…6 One of the major pathways involved in polarity decisions at this stage in the early embryo is Wnt/Fz which is engaged in spindle rotation of some of the dividing AB descendants ensuring correct contacts of daughter cells to neighboring blastomeres. [15][16][17] The relation of a LAT-1-mediated signal and a Wnt/Fz cascade remains unclear. It can be speculated that LAT-1 signaling acts in parallel of cues mediated by Wnt/Fz and aids its propagation.…”