Cell-Cycle-Coupled Oscillations in Apical Polarity and Intercellular Contact Maintain Order in Embryonic Epithelia

Abstract

Throughout animals, embryonic cells must ultimately organize into polarized epithelial layers that provide the structural basis for gastrulation or subsequent developmental events [1]. Precisely how this primary epithelium maintains continuous integrity during rapid and repeated cell divisions has never been directly addressed, particularly in cases where early cleavages are driven in synchrony. Representing the early-branching non-bilaterian phylum Cnidaria, embryos of the sea anemone Nematostella vectensis undergo rapid synchronous cell divisions and ultimately give rise to a diploblastic epithelial body plan after gastrulation [2, 3]. Here, using live imaging of apical polarity proteins in Nematostella embryos, we demonstrate that cell polarity is established by the four-cell stage and then reiteratively lost during subsequent mitoses, correlating with transient adhesion disengagement and dramatic deformations of embryonic morphology. Intriguingly, the re-establishment of polarity and adhesion during each interphase is associated with a process of whole-embryo compaction analogous to that observed in mammals [4-7]. Because similar protein dynamics are observed in dividing epithelial cells in Drosophila melanogaster, we propose that cell-cycle-coupled oscillations in apical polarity may be conserved throughout Metazoa.

Cadherin switch marks germ layer formation in the diploblastic sea anemone Nematostella vectensis

“…3). In contrast to the Par system proteins (Ragkousi et al, 2017;Salinas-Saavedra et al, 2018) we did not observe a loss of cell polarity marked by Cdh3 during early cell divisions ( Fig. 3).…”

Germ layer specific regulation of cell polarity and adhesion gives insight into the evolution of mesoderm

“…In bilaterians, AJs recruit members of the aPKC/Par complex and the direct interaction between Par-3 and aPKC/Par-6 is required for the maintenance and maturation of AJs (Ohno et al, 2015; Ragkousi, Marr, McKinney, Ellington, & Gibson, 2017). AJs are characterized by the binding between cadherins and ß-catenin: cadherins sequester ß-catenin from the cytoplasm to the cortex, making it unavailable for nuclear signaling and endomesoderm specification (Kumburegama, Wijesena, Xu, & Wikramanayake, 2011; Wikramanayake et al, 2003).…”

Surviving Acute Organ Failure: Cell Polyploidization and Progenitor Proliferation

“…However, widespread parenchymal cell dedifferentiation and/or proliferation would be largely counterproductive in acute organ failure because they imply a transient loss of specialized cellular functions. If the remnant parenchymal cells that sustain minimal residual function of an organ such as the heart, liver, or kidney were to undergo widespread mitosis, this would further reduce functional performance, which might become critical and, in the worst case, lead to death [16][17][18]. Indeed, cytoskeleton structure [16,17] and cell polarity [18] can be reiteratively lost during mitosis and cytokinesis, correlating with transient adhesion disengagement and dramatic deformation of organism morphology [18].…”

“…If the remnant parenchymal cells that sustain minimal residual function of an organ such as the heart, liver, or kidney were to undergo widespread mitosis, this would further reduce functional performance, which might become critical and, in the worst case, lead to death [16][17][18]. Indeed, cytoskeleton structure [16,17] and cell polarity [18] can be reiteratively lost during mitosis and cytokinesis, correlating with transient adhesion disengagement and dramatic deformation of organism morphology [18]. However, evolution has selected alternative solutions and minimized the mitotic ability of differentiated parenchymal cells [19,20].…”