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.

Figure 1. mirroring among single cells

(A–C) Actin cytoskeletal elements of daughter cells in culture showing a mirroring of the angle of filament orientation. (D,E) Sample migration tracks of cells in culture showing mirroring of cell paths after splitting. These data indicate the presence of chirality in single cells that is preserved at splitting, possibly providing a model for understanding enantiomer (bookending) of symmetry properties in monozygotic twins derived from early splitting of the egg. Images are used with permission of Albrecht Guenther-Buehler (Albrecht-Buehler, 1977).

Figure 2. bilateral gynandromorphy

(A) Papilio glaucus, used with permission from James K. Adams, showing boundary between male and female cells exactly down the midline. (B) A bilateral gynandromorph lobster, used with permission of the Bangor Daily News; photo by Abigail Curtis. (C) A CHILD syndrome patient with harlequin pigmentation, used with permission of John Wiley and Sons from the American Journal of Medical Genetics, 2000, 90: 340. (D) A gynandromophic blue crab, Callinectes sapidus (ventral view; left side of the body exhibiting the narrower abdomen typical of males), with permission from Rom Lipcius (VIMS); taken from (Kleps et al., 2007). (E) A section of the brain of a gynandromorphic finch processed for in situ hybridization with probes to sex-specific transcripts (dark signal = female chromosome, no signal = male chromosome), where expression of a molecular marker in the brain of a gynandromorphic finch reveals that the separation between male and female cells is exactly down the midline. Image taken from Fig. 6 of (Agate et al., 2003), copyright held by National Academy of Sciences of the United States.