fsi zebrafish show concordant reversal of laterality of viscera, neuroanatomy, and a subset of behavioral responses

Asymmetries in CNS neuroanatomy are assumed to underlie the widespread cognitive and behavioral asymmetries in vertebrates. Studies in humans have shown that the laterality of some cognitive asymmetries is independent of the laterality of the viscera; discrete mechanisms may therefore regulate visceral and neural lateralization. However, through analysis of visceral, neuroanatomical, and behavioral asymmetries in the frequent-situs-inversus (fsi) line of zebrafish, we show that the principal left-right body asymmetries are coupled to certain brain asymmetries and lateralized behaviors. fsi fish with asymmetry defects show concordant reversal of heart, gut, and neuroanatomical asymmetries in the diencephalon. Moreover, the neuroanatomical reversals in reversed fsi fish correlate with reversal of some behavioral responses in both fry and adult fsi fish. Surprisingly, two behavioral asymmetries do not reverse, suggesting that at least two separable mechanisms must influence functional lateralization in the CNS. Partial reversal of CNS asymmetries may generate new behavioral phenotypes; supporting this idea, reversed fsi fry differ markedly from their normally lateralized siblings in their behavioral response to a novel visual feature. Revealing a link between visceral and brain asymmetry and lateralized behavior, our studies help to explain the complexity of the relationship between the lateralities of visceral and neural asymmetries.     

Establishing a left-right axis in the embryo

Vertebrates exhibit evolutionarily conserved asymmetries in the pattern of internal organ placement that are essential for their normal physiological function. Left-right asymmetries in organ situs are dependent upon the formation of an intact left-right axis during embryogenesis. Recently many of the molecular components involved in the initiation and maintenance of the left-right axis have been described. These molecules and their function in promoting left-right asymmetries are reviewed.     

Asymmetries in visual texture discrimination

Recent results have shown that texture discrimination is an asymmetrical process; texture A within texture B may be much easier to detect than texture B within texture A. Two questions regarding discrimination asymmetries are addressed: (i) what sorts of textural properties are associated with discrimination asymmetries; and (ii) what sort of architecture would yield asymmetries. Two experiments show that discrimination asymmetries obtain when textures comprise circles of different sizes (large circles are easier to detect in small than vice versa) and when circles differ only in the regularity of their placement (irregularly placed circles are easier to detect in a background of regularly placed circles than vice versa). A plausible account of texture discrimination would involve the decomposition of images via a set orientation and scale selective filters followed by a second layer of filtering to detect energy differences between adjacent regions in the original convolutions. Discrimination asymmetries provide prima facie evidence against such a model because it involves only local measurements and comparisons. We propose that discrimination asymmetries are elegantly explained if it is assumed that the responses of the orientation and scale selective filters are normalized by the degree to which similarly tuned operators are responding elsewhere in the image; viz., global normalization of filter responses. However, there are cases where such global normalization is not required to explain asymmetrical discrimination.     

Age- and sex-associated variations in the directional asymmetry of rhesus macaque forelimb bones

Several investigators have questioned the significance of handedness as an explanation of directional forelimb asymmetries, yet little has been done to isolate other explanatory factors. In this investigation, we analyze 61 female and 76 male rhesus macaque skeletons for evidence of age- and/or sex-associated variations in ten forelimb bone measurements. All significant directional asymmetries are found to favor the right side. Although some of these asymmetries are found to favor the right side. Although some of these asymmetries are compatible with the interpretation of muscle hypertrophy associated with preferential use of the right forelimb, the overall pattern suggests that age- and sex-related ontogenetic factors deserve equal consideration. Significant sex differences in asymmetry means are present within and across age groups (juveniles, subadults, and adults), and numerous changes in asymmetry with age are also found. A pattern of decreasing asymmetry with age was found in males, with 40% of the ten measures being asymmetrical in juveniles, 30% in subadults, and 20% in adults. Among females, this pattern is reversed. No significant asymmetries were found for juvenile or subadult females, whereas 40% of the measures were asymmetrical in adult females. We conclude that greater consideration of age- and sex-related factors is necessary when drawing samples for the purpose of investigating asymmetries, and an awareness of trait-specific age and sex patterns of variation is necessary when citing forelimb asymmetries in demographically nonrepresentative populations as evidence of handedness or other behavioral asymmetries.     

Leaf asymmetry as a developmental constraint imposed by auxin-dependent phyllotactic patterning

In a majority of species, leaf development is thought to proceed in a bilaterally symmetric fashion without systematic asymmetries. This is despite the left and right sides of an initiating primordium occupying niches that differ in their distance from sinks and sources of auxin. Here, we revisit an existing model of auxin transport sufficient to recreate spiral phyllotactic patterns and find previously overlooked asymmetries between auxin distribution and the centers of leaf primordia. We show that it is the direction of the phyllotactic spiral that determines the side of the leaf these asymmetries fall on. We empirically confirm the presence of an asymmetric auxin response using a DR5 reporter and observe morphological asymmetries in young leaf primordia. Notably, these morphological asymmetries persist in mature leaves, and we observe left-right asymmetries in the superficially bilaterally symmetric leaves of tomato (Solanum lycopersicum) and Arabidopsis thaliana that are consistent with modeled predictions. We further demonstrate that auxin application to a single side of a leaf primordium is sufficient to recapitulate the asymmetries we observe. Our results provide a framework to study a previously overlooked developmental axis and provide insights into the developmental constraints imposed upon leaf morphology by auxin-dependent phyllotactic patterning.     

The ‘Goldilocks Zone’: Getting the Measure of Manual Asymmetries

Some studies have shown that manual asymmetries decrease in older age. These results have often been explained with reference to models of reduced hemispheric specialisation. An alternative explanation, however, is that hand differences are subtle, and capturing them requires tasks that yield optimal performance with both hands. Whereas the hemispheric specialisation account implies that reduced manual asymmetries should be reliably observed in older adults, the ‘measurement difficulty’ account suggests that manual asymmetries will be hard to detect unless a task has just the right level of difficulty—i.e. within the ‘Goldilocks Zone’, where it is not too easy or too hard, but just right. Experiment One tested this hypothesis and found that manual asymmetries were only detected when participants performed in this zone; specifically, performance on a tracing task was only superior in the preferred hand when task constraints were high (i.e. fast speed tracing). Experiment Two used three different tasks to examine age differences in manual asymmetries; one task produced no asymmetries, whilst two tasks revealed asymmetries in both younger and older groups (with poorer overall performance in the old group across all tasks). Experiment Three revealed task-dependent asymmetries in both age groups, but highlighted further detection difficulties linked with the metric of performance and compensatory strategies used by participants. Results are discussed with reference to structural learning theory, whereby we suggest that the processes of inter-manual transfer lead to relatively small performance differences between the hands (despite a strong phenomenological sense of performance disparities).     

Fluctuation and directional asymmetry of the oppositely orientated finger ridge counts in Bulgarians

In a sample from Northeast Bulgaria (500 males, 500 females) fluctuating and directional asymmetries of the radial and ulnar finger ridge-counts were studied, each sex separately and finger-by-finger. Neither the ridge counts nor their fluctuating asymmetries show any considerable sex difference. In contrast, the curves of the ulnar and radial directional asymmetries, each of them being similarly distributed over the digits in both sexes, are contrasted in males and females. One interpretation is that the sex chromosomes exert a considerable effect upon the mediolateral developmental gradients and so cause a set of well expressed sex differences in the directional asymmetries of the ulnar and radial finger ridge-counts.     

Left-right asymmetry in the vertebrate embryo: from early information to higher-level integration

Although vertebrates seem to be essentially bilaterally symmetrical on the exterior, there are numerous interior left-right asymmetries in the disposition and placement of internal organs. These asymmetries are established during embryogenesis by complex epigenetic and genetic cascades. Recent studies in a range of model organisms have made important progress in understanding how this laterality information is generated and conveyed to large regions of the embryo. Both commonalities and divergences are emerging in the mechanisms that different vertebrates use in left-right axis specification. Recent evidence also provides intriguing links between the establishment of left-right asymmetries and the symmetrical elongation of the anterior-posterior axis.     

Persistence of subtle departures from symmetry over multiple molts in individual brachyuran crabs: Relevance to developmental stability

Fluctuating asymmetry (FA) is generally viewed as a population-level character. It is described by some measure of the variance of the difference between the right and left sides for a collection of individuals. Very little is known of the developmental origins of FA, despite the fact that FA is widely used to estimatedevelopmental stability. We present a novel technique for examining the growth trajectory of the asymmetries that give rise to FA, and we explore two sample data sets for the brachyuran crabHemigrapsus nudus. We have traced the fate of these small, random deviations from perfect symmetry through three successive molts of individual crabs. Invertebrates that molt, and hence grow in discrete steps, provide an easily preserved record of their growth. Model II regressions of measurements from one molt versus the previous molt can help describe the stability of subtle departures from symmetry over time. Although any number of different patterns may occur, we identify four general cases: a) asymmetries vary at random throughout growth (random determination), b) asymmetries remain unchanged in sign and magnitude (constant asymmetries), c) asymmetries increase in proportion to character size and hence increase with growth (size-dependent asymmetries), and d) asymmetries persist, but are reduced in magnitude (damped asymmetries). Data from tenHemigrapsus nudus, measured for between 21 and 28 metrical, limb-segment characters over three successive molts, yielded associations most similar to our pattern ‘b’, although some subtle departures in the direction of pattern ‘c’ were also observed. Persistent asymmetries accounted for 26% and 20% of the variance among asymmetries between molts 1 and 2, and molts 2 and 3 respectively. Thus, in spite of large and rapid increments in the external size of the crab, these subtle asymmetries tended to persist in both direction and magnitude, from molt to molt. This result suggests either i) that individual crabs have a genetic predisposition towards asymmetry in a particular direction but contribute to a continuous and normal distribution ofR-L differences at the population level, or ii) that these subtle asymmetries arose at some earlier ontogenetic stage and were preserved through growth. Either interpretation has important ramifications for the study of FA. The first suggests that under some circumstances FA may not provide a valid measure of developmental instability, because subtle departures from symmetry in an individual may have a genetic basis. The second implies that subtle departures from bilateral symmetry are not ‘corrected’ as an individual grows.     

Brain asymmetries in face processing: a critical review of electrophysiological studies from a psychological point of view

The few studies dealing with physiological (EEG, VEP) brain asymmetries in the processing of faces by neurologically intact subjects are critically reviewed from a psychological point of view. It emerges that a more careful selection of the cognitive tasks is needed, along with more prudent statistical planning. The difficulties of comparing physiological and behavioral asymmetries are also emphasized.     

Left and right in the amphibian world: which way to develop and where to turn?

The last decade has seen a dramatic increase in studies on the development, function and evolution of asymmetries in vertebrates, including amphibians. Here we discuss current knowledge of behavioral and anatomical asymmetries in amphibians. Behavioral laterality in the response of both adult and larval anurans to presumed predators and competitors is strong and may be related, respectively, to laterality in the telencephalon of adults and the Mauthner neurons of tadpoles. These behavior lateralities, however, do not seem to correlate with visceral asymmetries in the same animals. We briefly compare what is known about the evolution and development of asymmetry in the structure and function of amphibians with what is known about asymmetries in other chordate and non-chordate groups. Available data suggest that the majority of asymmetries in amphibians fall into two independent groups: (1) related to situs viscerum and (2) of a neurobehavioral nature. We find little evidence linking these two groups, which implies different developmental regulatory pathways and independent evolutionary histories for visceral and telencephalic lateralizations. Studies of animals other than standard model species are essential to test hypotheses about the evolution of laterality in amphibians and other chordates.     

Brief communication: Locomotor limb preferences in captive chimpanzees (Pan troglodytes): implications for morphological asymmetries in limb bones

Understanding the evolutionary origins of hemispheric specialization remains a topic of considerable interest in a variety of scientific disciplines. Whether nonhuman primates exhibit population-level limb preferences continues to be a controversial topic. In this study, limb preferences for ascending and descending locomotion were assessed as a means of examining the hypothesis that asymmetries in forelimb bones might be attributed to asymmetries in posture. The results indicated that captive chimpanzees showed a population-level leftward asymmetry in descending locomotion but no group bias for ascending locomotion. The results are consistent with previous behavioral studies in captive chimpanzees as well as studies on skeletal asymmetries of the forelimbs of chimpanzees.     

PAR proteins and the cytoskeleton: a marriage of equals

The PAR proteins are a group of widely conserved regulators of polarity, many of which are asymmetrically localized in polarized cells. Recent work shows that distinct modes of actomyosin- and microtubule-based transport contribute to the establishment of PAR asymmetries in different cell types. Cross-regulatory interactions among PAR proteins and with other conserved polarity complexes stabilize asymmetries once they form, and shape the evolution of PAR protein distributions in response to cytoskeletal transport or other polarizing inputs. The PAR proteins in turn modulate the actomyosin and microtubule cytoskeletons. In some cases, this is a form of feedback control, central to the establishment and maintenance of PAR asymmetries. In others, it underlies the elaboration of functional cell polarity.     

Left-right patterning from the inside out: widespread evidence for intracellular control

The field of left-right (LR) patterning--the study of molecular mechanisms that yield directed morphological asymmetries in otherwise symmetrical organisms--is in disarray. On one hand is the undeniably elegant hypothesis that rotary beating of inclined cilia is the primary symmetry-breaking step: they create an asymmetric extracellular flow across the embryonic midline. On the other hand lurk many early symmetry-breaking steps that, even in some vertebrates, precede the onset of ciliary flow. We highlight an intracellular model of LR patterning where gene expression is initiated by physiological asymmetries that arise from subcellular asymmetries (e.g. motor-protein function along oriented cytoskeletal tracks). A survey of symmetry breaking in eukaryotes ranging from protists to vertebrates suggests that intracellular cytoskeletal elements are ancient and primary LR cues. Evolutionarily, quirky effectors like ciliary motion were likely added later in vertebrates. In some species (like mice), developmentally earlier cues may have been abandoned entirely. Late-developing asymmetries pose a challenge to the intracellular model, but early mid-plane determination in many groups increases its plausibility. Multiple experimental tests are possible.