C. elegansGATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells

Abstract

SUMMARYThe C. elegans seam cells are lateral epithelial cells arrayed in a single line from anterior to posterior that divide in an asymmetric, stem cell-like manner during larval development. These asymmetric divisions are regulated by Wnt signaling; in most divisions, the posterior daughter in which the Wnt pathway is activated maintains the progenitor seam fate, while the anterior daughter in which the Wnt pathway is not activated adopts a differentiated hypodermal fate. Using mRNA tagging and microarray analysis, we identified the functionally redundant GATA factor genes egl-18 and elt-6 as Wnt pathway targets in the larval seam cells. EGL-18 and ELT-6 have previously been shown to be required for initial seam cell specification in the embryo. We show that in larval seam cell asymmetric divisions, EGL-18 is expressed strongly in the posterior seam-fated daughter. egl-18 and elt-6 are necessary for larval seam cell specification, and for hypodermal to seam cell fate transformations induced by ectopic Wnt pathway overactivation. The TCF homolog POP-1 binds a site in the egl-18 promoter in vitro, and this site is necessary for robust seam cell expression in vivo. Finally, larval overexpression of EGL-18 is sufficient to drive expression of a seam marker in other hypodermal cells in wild-type animals, and in anterior hypodermal-fated daughters in a Wnt pathway-sensitized background. These data suggest that two GATA factors that are required for seam cell specification in the embryo independently of Wnt signaling are reused downstream of Wnt signaling to maintain the progenitor fate during stem cell-like divisions in larval development. KEY WORDS: C. elegans, Wnt signaling, Asymmetric cell divisionC. elegans GATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells

The tumor suppressor APC differentially regulates multiple beta-catenins through the function of Axin and casein kinase 1alpha during C. elegans asymmetric stem cell divisions

“…These visually accessible cells repeatedly divide asymmetrically in a stem-cell-like pattern during larval development, and cell fate determination for each of these divisions is dependent on the WbA pathway (supplementary material Fig. S1; Mizumoto and Sawa, 2007;Kanamori et al, 2008;Huang et al, 2009;Banerjee et al, 2010;Gleason and Eisenmann, 2010;Ren and Zhang, 2010;Harterink et al, 2011;Yamamoto et al, 2011;Gorrepati et al, 2013;Hughes et al, 2013). Thus, the lineage maintains a constant number of seam cells (posterior WbA-signaled daughters) while increasing the number of hypodermal nuclei (anterior Wnt-independent daughters).…”

“…Activation or repression of WbA results in increased or decreased seam cell numbers, respectively. At least one direct target of SYS-1 and POP-1, EGL-18, is also differentially expressed in the seam daughters; EGL-18 expression is elevated in the posterior cell with a high SYS-1:POP-1 ratio and is reduced or absent in the anterior daughter with a low SYS-1:POP-1 ratio (Gorrepati et al, 2013). Other recent studies have analyzed the genetics of Wnt signaling components in C. elegans and the effects these components have on seam cell number, providing several potential regulators of SYS-1 asymmetry (Huang et al, 2009;Banerjee et al, 2010;Gleason and Eisenmann, 2010;Ren and Zhang, 2010).…”

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

“…While we have mainly studied components of the inhibitory side of the genetic network, it is still unclear what transcription factor(s) are primarily responsible for the activation of eff-1. Most mutations that alter the frequency of the P3.p hyp7/fusion cell fate lie in proteins that act as inhibitors to the cell fusion process, such as most Wnt pathway components, ceh-20, ref-1, ref-2, egl-18/elt-5, dyamin-1,andrab-5 (Alper andKenyon, 2001, 2002;Gorrepati et al, 2013;Koh et al, 2002;Smurova and Podbilewicz, 2016). Fewer have been found that are required for eff-1 activation, which could also provide additional noise or variability into the cell fate decision.…”

“…Studies have shown a lin-22 loss-of-function mutation decreases P3.p cell fusion frequencies (Katsanos et al, 2017;Schlager et al, 2006). LIN-22 codes for a Hairy/Enhancer of Split-related transcription factor, which was found to act in the Wnt pathway by repressing egl-18, a GATA transcription factor, also a repressor of cell fusion in the seam cells (Gorrepati et al, 2013;Katsanos et al, 2017;Wrischnik and Kenyon, 1997). Therefore, variations in not only the inhibitor molecules, but LIN-22 could create noise and variability that leads to stochastic eff-1 expression and cell fusion.…”

Asymmetric Wnt Pathway Signaling Facilitates Stem Cell-Like Divisions via the Nonreceptor Tyrosine Kinase FRK-1 inCaenorhabditis elegans

“…Gorrepati et al (2013) reported that EGL-18 overexpression in a Wnt-sensitized background is capable of activating seam cell marker expression in head and ventral hypodermis and that EGL-18 is required for seam cell fate specification. It has also been previously reported that frk-1 acts upstream of elt-18 and elt-3 in regulating hypodermal cell specification during embryonic development (Putzke et al 2005).…”