A Wnt Signaling System that Specifies Two Patterns of Cell Migration in C. elegans

Abstract

In C. elegans, a bilateral pair of neuroblasts, QL and QR, give rise to cells that migrate in opposite directions along the anteroposterior (A/P) body axis. QL and its descendants migrate posteriorly whereas QR and its descendants migrate anteriorly. We find that a Wnt family member, EGL-20, acts in a dose-dependent manner to specify these opposite migratory behaviors. High levels of EGL-20 promote posterior migration by activating a canonical Wnt signal transduction pathway, whereas low levels promote anterior migration by activating a separate, undefined pathway. We find that the two Q cells respond differently to EGL-20 because they have different response thresholds. Thus, in this system two distinct dose-dependent responses are specified not by graded levels of the Wnt signal, but instead by left-right asymmetrical differences in the cellular responsiveness to Wnt signaling.

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

“…All five Wnts are also expressed during larval life in discrete locations along the anteriorposterior axis: The Wnts LIN-44, EGL-20, and CWN-1 are expressed in a nested pattern in the posterior, whereas CWN-2 is expressed in more anterior cells (Fig. 2) (Herman et al 1995;Whangbo and Kenyon 1999;Coudreuse et al 2006;Gleason et al 2006;Pan et al 2006;Kennerdell et al 2009;Song et al 2010;Harterink et al 2011;Yamamoto et al 2011). 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).…”

“…In the more sensitive QL neuroblast, exposure to EGL-20 leads to Wnt/b-catenin pathway activation, expression of the Hox gene mab-5, and posterior migration of progeny, whereas the less sensitive QR neuroblast and its progeny do not express mab-5 and continue to migrate toward the anterior (Fig. 3B) (Salser and Kenyon 1992;Whangbo and Kenyon 1999). Loss of function of the positively acting WBC pathway genes mig-14/Wntless, vps-35/retromer, egl-20/Wnt, lin-17/Fz, mig-1/Fz, mig-5/Dsh, bar-1/b-cat, and pop-1/TCF, or overexpression of the negative regulators gsk-3/GSK3b and pry-1/Axin, leads to loss of mab-5 expression and the anterior migration of the QL.d cells (Fig.…”

Wnt signaling establishes anteroposterior neuronal polarity and requires retromer inC. elegans

“…EGL-20 controls cell fate specification and posterior migration of the neuroblast QL and its descendants, such as PVM, by upregulating expression of HOX gene mab-5 (Harris et al, 1996;Whangbo and Kenyon, 1999). egl-20 mutations block mab-5::gfp expression in QL and its descendants and both mab-5 and egl-20 mutations cause PVM to migrate anteriorly rather than posteriorly.…”

“…elegans has five Wnts [CWN-1, CWN-2, EGL-20, LIN-44 and MOM-2 (Shackleford et al, 1993;Herman et al, 1995;Thorpe et al, 1997;Whangbo and Kenyon, 1999)], four Frizzleds [CFZ-2, LIN-17, MIG-1 and MOM-5 (Sawa et al, 1996;Rocheleau et al, 1997;Zinovyeva and Forrester, 2005;Pan et al, 2006)] and a single Ryk, LIN-18 (Inoue et al, 2004). Wnt signaling establishes the polarity of asymmetric cell divisions, determines cell fates and guides cell migrations (Korswagen, 2002;Herman, 2002).…”

Variability in β-catenin pulse dynamics in a stochastic cell fate decision inC. elegans

“…The Wnt/β-catenin pathway has been intensively studied in C. elegans, with a significant focus on Wnt-guided cell migration and the SYS-1/POP-1 Wnt asymmetry pathway, required for proper fate of seam cells and some neurons, while the role of BAR-1 in the Pn.p cells has remained less characterized (Eisenmann et al, 1998;Gleason et al, 2002;Harterink et al, 2011;Korswagen, 2002;Lin et al, 1998;Maloof et al, 1999;Mentink et al, 2014;Mila et al, 2015;Park and Priess, 2003;Shetty et al, 2005;Whangbo and Kenyon, 1999). While genetic evidence shows that β-catenin/BAR-1 is an inhibitor of the eff-1 gene, it is conventionally known to act as a transcriptional co-activator with the TCF/POP-1 protein, suggesting that the effect BAR-1 has on eff-1 is through another intermediate protein.…”