Rac1/RhoA antagonism defines cell-to-cell heterogeneity during epidermal morphogenesis in nematodes

Abstract

Antagonism between the GTPases Rac1 and RhoA controls different morphogenetic processes during embryonic development. Martin et al. use quantitative imaging analyses to demonstrate that cell-autonomous antagonism between the RhoA- and Rac1-like pathways defines cell-to-cell heterogeneity during epidermal morphogenesis in Caenorhabditis elegans.

Game of Tissues: How the Epidermis Thrones C. elegans Shape

“…They showed that dorsal cells use the RAC-1 mediated pathway to generate lamellipodia-like protrusions below the level of the CeAJs towards the seam cells while the seam cells use the RHO-1 mediated pathway to induce the formation of amoeboid-like protrusions in the direction of the dorsal cells. At the same time, the myosin activity controlled by these pathways regulates the remodeling of the CeAJs, where an increased myosin activity correlates with a decreased junctional length [84,85]. Thus, while the cells are restructuring their apical junctions, the basolateral membranes are relieving the tension generated in CeAJs through protrusive activity [85].…”

“…At the same time, the myosin activity controlled by these pathways regulates the remodeling of the CeAJs, where an increased myosin activity correlates with a decreased junctional length [84,85]. Thus, while the cells are restructuring their apical junctions, the basolateral membranes are relieving the tension generated in CeAJs through protrusive activity [85]. In accordance, a FRET-based force sensor placed in the HMP-1 gene, revealed that the tension exerted at the CeAJs decrease by 1.3-to 1.5-fold even though cells are experiencing high actomyosin contraction, supporting the idea that membrane protrusion acts as a tension relieving mechanism [54,[84][85][86].…”

Heterogeneity in heat shock response dynamics caused by translation fidelity decline and proteostasis collapse

“…Besides lifespan, heterogeneity has been observed and studied in C. elegans for various phenotypes, such as cell fate [15], cell morphogenesis [16], synthetic lethality [17], microbiome-host interactions [18], body size [19], developmental speed [19], number of offspring [19], stress responses [20,21], redox potential [22], and behaviour [23]. Of particular pertinence to the current study is the heterogeneity in the heat shock response (HSR), which has been tied to variability in lifespan, where a stronger HSR is indicative of longer lifespans among isogenic C. elegans [20].…”

Rac and Rho compete to cooperate

“…Yet, within individual cells, these two pathways tend to antagonize each other. resolve this conundrum by analyzing the behavior of individual epidermal cells during embryonic elongation (1).…”

“…Led by graduate student Emmanuel Martin, Jenna and colleagues developed a quantitative imaging method to measure the reorganization of individual epidermal cell junctions in elongating C. elegans embryos (1). By comparing embryos lacking either let-502 , pix-1 , or pak-1 , Martin et al determined that the Rho-like, let-502 -dependent pathway controls the remodeling of junctions between lateral epidermal cells, whereas Rac-like, pix-1 – and pak-1 –dependent signaling regulates junction remodeling in dorsal epidermal cells at the embryo’s anterior.…”