TheC. elegansembryonic fate specification factor EGL-18 (GATA) is reutilized downstream of Wnt signaling to maintain a population of larval progenitor cells

Abstract

In metazoans, stem cells in developing and adult tissues can divide asymmetrically to give rise to a daughter that differentiates and a daughter that retains the progenitor fate. Although the short-lived nematode C. elegans does not possess adult somatic stem cells, the lateral hypodermal seam cells behave in a similar manner: they divide once per larval stage to generate an anterior daughter that adopts a non-dividing differentiated fate and a posterior daughter that retains the seam fate and the ability to divide further. Wnt signaling pathway is known to regulate the asymmetry of these divisions and maintain the progenitor cell fate in one daughter, but how activation of the Wnt pathway accomplished this was unknown. We describe here our recent work that identified the GATA transcription factor EGL-18 as a downstream target of Wnt signaling necessary for maintenance of a progenitor population of larval seam cells. EGL-18 was previously shown to act in the initial specification of the seam cells in the embryo. Thus the acquisition of a Wnt-responsive cis-regulatory module allows an embryonic fate specification factor to be reutilized later in life downstream of a different regulator (Wnt signaling) to maintain a progenitor cell population. These results support the use of seam cell development in C. elegans as a simple model system for studying stem and progenitor cell biology.

Phenotypic Robustness of Epidermal Stem Cell Number in C. elegans Is Modulated by the Activity of the Conserved N-acetyltransferase nath-10/NAT10

“…In concurrence with the mRNA changes observed by smFISH, we found an increase in the egl-18 reporter expression and variability at the asymmetric division during the L2 stage when animals are exposed to nath-10 RNAi compared to empty vector control ( Figures 5E,F ). Since egl-18 is known to play a role in seam cell fate acquisition ( Gorrepati and Eisenmann, 2015 ), the increase in egl-18 expression in nath-10 mutants may be indicative of ectopic Wnt target activation and adoption of seam cell fate. This effect is likely to explain seam cell gains, which are somewhat more frequent than seam cell losses in nath-10(icb102) mutant populations (91 errors in 335 animals out of which 67 are seam cell gains and 24 are seam cell losses).…”

“…A number of other transcription factors and signaling pathways have been found to regulate seam cell development. GATA transcription factors, such as elt-1 and egl-18 , the engrailed homolog ceh-16 and the Runx / CBF β homologs rnt-1 / bro-1 are thought to be key players in the seam cell gene network ( Smith et al, 2005 ; Huang et al, 2009 ; Gorrepati et al, 2013 ; Gorrepati and Eisenmann, 2015 ). During seam cell patterning, the Wnt pathway activates targets necessary for seam cell maintenance, such as egl-18 , through the downstream effector POP-1/TCF, while ectopic egl-18 activation can drive ectopic seam cell fate retention ( Gorrepati et al, 2013 ).…”

Wnt Signaling Polarizes C. elegans Asymmetric Cell Divisions During Development

“…Seam cell fate acquisition is dependent on active WβA signaling where the signaled posterior seam cell daughter exhibits the characteristic high nuclear localization of SYS-1 and lowered POP-1 and the unsignaled hypodermal cell with a lower nuclear SYS-1 localization but higher POP-1 (Banerjee et al, 2010, Gleason and Eisenmann, 2010, Mizumoto and Sawa, 2007a). The signaled posterior daughter maintains its seam cell fate by upregulating EGL-18 and ELT-6 GATA factors, which are repressed in the unsignaled anterior daughter (Gorrepati et al, 2013, Gorrepati and Eisenmann, 2015, Gorrepati et al, 2015). …”

Wnt signaling and β-catenin regulation during asymmetric cell division in Caenorhabditis elegans

“…Our first result, that DSH-2 and MIG-5 are negative regulators of seam cell fate specification, was surprising. Previous experiments have shown that specification of the seam cell fate requires Wnt-dependent activation of the GATA factor EGL-18 in the posterior daughter, and as Dvl is generally considered to be a positive regulator of Wnt-dependent gene activation, these results seem incongruous (Gao and Chen, 2010;Gorrepati and Eisenmann, 2015;Gorrepati et al, 2013). However, delving into downstream effectors revealed that this result represents more a wrinkle in WβA signaling than it does a major departure from canonical Wnt/β-catenin signaling.…”