Possible Origins of Macroscopic Left-Right Asymmetry in Organisms

Abstract

I consider the microscopic mechanisms by which a particular leftright (L/R) asymmetry is generated at the organism level from the microscopic handedness of cytoskeletal molecules. In light of a fundamental symmetry principle, the typical pattern-formation mechanisms of diffusion plus regulation cannot implement the "right-hand rule"; at the microscopic level, the cell's cytoskeleton of chiral filaments seems always to be involved, usually in collective states dirven by polymerization forces or molecular motors. It seems particularly easy for handedness to emerge in a shear or rotation in the background of an effectively two-dimensional system, such as the cell membrane or a layer of cells, as this requires no pre-existing axis apart from the layer normal. I detail a scenario involving actin/myosin layers in snails and in C. elegans, and also one about the microtubule layer in plant cells. I also survey the other examples that I am aware of, such as the emergence of handednes such as the emergence of handednes in neurons, in eukaryote cell motility, and in non-flagellated bacteria.

Cell Chirality Induces Collective Cell Migration in Epithelial Sheets

“…Chiral behavior of cells has been reported elsewhere recently [25][26][27] and has been linked to chirally asymmetric dynamics of parts of the cytoskeleton, such as the actomyosin cortex beneath cell-surface membranes [28,29]. More recently, chiral mechanical torque generation in cells has been reported in C. elegans, which contributes to the formation of the left-right body axis [30].…”

What determines direction of asymmetry: genes, environment or chance?

“…One common theme emerges from studies of molecular mechanisms: asymmetry at the macroscopic level can often be traced back to subcellular (e.g. cytoskeletal) asymmetries, a connection expected on theoretical grounds [10,14,15]. But these studies focus almost exclusively on model taxa with fixed asymmetries (little or no variation within species) where development of asymmetry is deterministic.…”

A set of simple cell processes are sufficient to model spiral cleavage

“…1A) In spiralians, any cell division after the third round of division tends to be perpendicular to the previous cell division. This has been suggested as an explanation for the left-right alternation of cell divisions after the 4-cell stage (Guerrier, 1970;Meshcheryakov and Beloussov, 1975;Henley, 2012). This rule has been proposed to be a consequence of the stereotypic duplication and migration of the centrioles (which form a 90°angle between them) between cell divisions, that, in turn, biases the position of the mitotic spindle towards perpendicularity (Théry and Bornens, 2006;Minc and Piel, 2012).…”

“…A number of developmental processes have been hypothesized to explain spiral cleavage. Some are roughly understood as developmental rules by which the direction of the cell division plane is determined during cleavage (Freeman and Lundelius, 1982), whereas others are processes of mechanical cell interaction that lead to cell displacement during cleavage (Meshcheryakov and Beloussov, 1975;Wandelt and Nagy, 2004;Henley, 2012). Here, we refer to these hypotheses as 'developmental rules of division plane specification', or, simply, 'rules'.…”

“…1B) According to Meshcheryakov's and related studies (Meshcheryakov and Beloussov, 1975;Wandelt and Nagy, 2004;Henley, 2012), blastomeres in spiral embryos rotate over themselves immediately after cell division. Rotating over themselves means that all the cell parts radially move with respect to an static rotation axis crossing .…”