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

Abstract

Individual cells and organisms experience perturbations from internal and external sources, yet manage to buffer these to produce consistent phenotypes, a property known as robustness. While phenotypic robustness has often been examined in unicellular organisms, it has not been sufficiently studied in multicellular animals. Here, we investigate phenotypic robustness in Caenorhabditis elegans seam cells. Seam cells are stem cell-like epithelial cells along the lateral edges of the animal, which go through asymmetric and symmetric divisions contributing cells to the hypodermis and neurons, while replenishing the stem cell reservoir. The terminal number of seam cells is almost invariant in the wild-type population, allowing the investigation of how developmental precision is achieved. We report here that a loss-of-function mutation in the highly conserved N-acetyltransferase nath-10/NAT10 increases seam cell number variance in the isogenic population. RNA-seq analysis revealed increased levels of mRNA transcript variability in nath-10 mutant populations, which may have an impact on the phenotypic variability observed. Furthermore, we found disruption of Wnt signaling upon perturbing nath-10 function, as evidenced by changes in POP-1/TCF nuclear distribution and ectopic activation of its GATA transcription factor target egl-18. These results highlight that NATH-10/NAT-10 can influence phenotypic variability partly through modulation of the Wnt signaling pathway.

Probing small ribosomal subunit RNA helix 45 acetylation across eukaryotic evolution

“…The evolutionary forces that drove disappearance of rRNA acetylation in C. elegans remain unknown. Nonetheless, our results indicate that the changes in robustness of vulval cell-fate specification observed when the essential nath10 gene ( 45 , 46 ) was mutated did not reflect loss of rRNA modification but more likely the involvement of nath10 in pre-rRNA processing and/or tRNA acetylation. A similar conclusion was reached recently when it was shown that the involvement of Fibrillarin in neural crest cell maturation of Xenopus laevis depends on its role in pre-rRNA processing rather than in methylation ( 47 ).…”

Gene expression profiling of epidermal cell types in C. elegans using Targeted DamID

“…To produce a seam cell hda-1 hairpin construct, a fragment from the hda-1 gene overlapping the 2 nd and 3 rd exons was amplified using oligos DK247 and DK248. The amplicon was inserted with a Golden Gate reaction in pDK157 ( srf-3i1-mut::Δpes-10::outron::non-palGGBpiI::srf-3a intron5::non-paIGGEsp3I::p10 3’UTR ) ( Hintze et al, 2021 )) to produce pDK158( srf-3i1-mut::Δpes-10::outron::>hda-1 fragment>::srf-3a intron5::<hda-1 fragment<::p10 3’UTR ).…”

Canalization of Phenotypes—When the Transcriptome is Constantly but Weakly Perturbed

“…The first one is to measure the variance of phenotypic values at a particular stage of development. Such measurements of phenotypic robustness have been frequently adopted in the literature ( Levy and Siegal 2008 ; Kasper et al 2017 ; Hintze et al 2021 ), and reviews ( Rendel 1967 ; Félix and Barkoulas 2015 ; Takahashi 2019 ). A second approach, taken in this study, is to follow the development to the final stages (i.e., maturation to adulthood and death) as Waddington envisaged ( Wagner 2005 ).…”