What's left in asymmetry?

Abstract

Left-right patterning is a fascinating problem of morphogenesis, linking evolutionary and cellular signaling mechanisms across many levels of organization. In the past 15 years, enormous progress has been made in elucidating the molecular details of this process in embryos of several model species. While many outside the field seem to believe that the fundamental aspects of this pathway are now solved, workers on asymmetry are faced with considerable uncertainties over the details of specific mechanisms, a lack of conceptual unity of mechanisms across phyla, and important questions that are not being pursued in any of the popular model systems. Here, we suggest that data from clinical syndromes, cryptic asymmetries, and bilateral gynandromorphs, while not figuring prominently in the mainstream work on LR asymmetry, point to crucial and fundamental gaps of knowledge about asymmetry. We identify 12 big questions that provide exciting opportunities for fundamental new advances in this field.

Left-Right Symmetry Breaking in Tissue Morphogenesis via Cytoskeletal Mechanics

“…7 In vivo examples include drosophila hindgut rotation 8 and the coherent orientation of cardiomyocytes, which form individual concentric layers of fibers, with incrementally increasing angle in each layer from the epicardium to the endocardium. 34 At a broader level, this robust capacity of differentiated cells to self-organize into multicellular structures with LR asymmetric alignment may have a fundamental role in embryogenesis and postnatal development, allowing cell-based engineering of regenerative tissues that are architecturally and functionally more authentic than previously possible.…”

“…Another model is that LR asymmetry is motivated by intracellular events originated by cytoplasmic organization at an even earlier stage. 2 Recently, cytoskeletal chirality and planar cell polarity were shown to specify the LR axis at early embryogenesis, 3-6 suggesting that LR asymmetry is coordinated by single- or multi-cell organizers and propagates through the rest of the tissue architecture, 7 as evidenced by epithelial cell chirality underlying the hindgut rotation 8 and chiral movement of blastomeres. 6 Thus, to organize LR asymmetry at multiscale levels of morphogenesis, cells with chirality must also be present in adequate numbers.…”

Characterization of cellular mechanical torque by rotation of ferromagnetic nanowire

“…In most animals, the internal organ is LR asymmetrically distributed [1]. At microscale, the contractility of heart requires the cardiac fibers assembling into layers of muscle with specific orientation angles [5].…”

“…Left-right asymmetry (LR) is a ubiquitous feature in many phases of tissue formation [1][2][3][4]. In most animals, the internal organ is LR asymmetrically distributed [1].…”

Polarity proteins are required for left–right axis orientation and twin–twin instruction

“…While considerable insight has been generated into the molecular mechanisms of patterning along the anterior-posterior and dorsal-ventral axes, much remains to be understood about how the LR axis is consistently oriented with respect to the other two (Aw and Levin, 2008, 2009; Levin, 2005, 2006; Speder et al , 2007; Tabin, 2005; Vandenberg and Levin, 2010b). Externally, the vertebrate body-plan possesses bilateral symmetry, but this is coupled with a strikingly conserved LR asymmetry of the internal organs including the morphogenesis and placement of the heart, liver, gall bladder, stomach and lungs.…”