Cosegregation of asymmetric features during cell division

Cellular asymmetry plays a major role in the ageing and evolution of multicellular organisms. However, it remains unknown how the cell distinguishes ‘old’ from ‘new’ and whether asymmetry is an attribute of highly specialized cells or a feature inherent in all cells. Here, we investigate the segregation of three asymmetric features: old and new DNA, the spindle pole body (SPB, the centrosome analogue) and the old and new cell ends, using a simple unicellular eukaryote, Schizosaccharomyces pombe . To our knowledge, this is the first study exploring three asymmetric features in the same cells. We show that of the three chromosomes of S. pombe , chromosome I containing the new parental strand, preferentially segregated to the cells inheriting the old cell end. Furthermore, the new SPB also preferentially segregated to the cells inheriting the old end. Our results suggest that the ability to distinguish ‘old’ from ‘new’ and to segregate DNA asymmetrically are inherent features even in simple unicellular eukaryotes.

Chirality of the cytoskeleton in the origins of cellular asymmetry

Self-assembly of two important components of the cytoskeleton of eukaryotic cells, actin microfilaments and microtubules (MTs) results in polar filaments of one chirality. As is true for bacterial flagella, in actin microfilaments, screw direction is important for assembly processes and motility. For MTs, polar orientation within the cell is paramount. The alignment of these elements in the cell cytoplasm gives rise to emergent properties, including the potential for cell differentiation and specialization. Complex MTs with a characteristic chirality are found in basal bodies and centrioles; this chirality is preserved in cilia. In motile cilia, it is reflected in the direction of the effective stroke. The positioning of the basal body or cilia on the cell surface depends on polarity proteins. In evolution, survival depends on global polarity information relayed to the cell in part by orientation of the MT and actin filament cytoskeletons and the chirality of the basal body to determine left and right coordinates within a defined anterior–posterior cell and tissue axis. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

Control of stem cell self-renewal and differentiation by the heterochronic genes and the cellular asymmetry machinery in Caenorhabditis elegans

Transitions between asymmetric (self-renewing) and symmetric (proliferative) cell divisions are robustly regulated in the context of normal development and tissue homeostasis. To genetically assess the regulation of these transitions, we used the postembryonic epithelial stem (seam) cell lineages of Caenorhabditis elegans. In these lineages, the timing of these transitions is regulated by the evolutionarily conserved heterochronic pathway, whereas cell division asymmetry is conferred by a pathway consisting of Wnt (Wingless) pathway components, including posterior pharynx defect (POP-1)/TCF, APC related/adenomatosis polyposis coli (APR-1)/APC, and LIT-1/NLK (loss of intestine/Nemo-like kinase). Here we explore the genetic regulatory mechanisms underlying stage-specific transitions between self-renewing and proliferative behavior in the seam cell lineages. We show that mutations of genes in the heterochronic developmental timing pathway, including lin-14 (lineage defect), lin-28, lin-46, and the lin-4 and let-7 (lethal defects)-family microRNAs, affect the activity of LIT-1/POP-1 cellular asymmetry machinery and APR-1 polarity during larval development. Surprisingly, heterochronic mutations that enhance LIT-1 activity in seam cells can simultaneously also enhance the opposing, POP-1 activity, suggesting a role in modulating the potency of the cellular polarizing activity of the LIT-1/POP-1 system as development proceeds. These findings illuminate how the evolutionarily conserved cellular asymmetry machinery can be coupled to microRNA-regulated developmental pathways for robust regulation of stem cell maintenance and proliferation during the course of development. Such genetic interactions between developmental timing regulators and cell polarity regulators could underlie transitions between asymmetric and symmetric stem cell fates in other systems and could be deregulated in the context of developmental disorders and cancer.