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.     

Testis asymmetry in birds: the influences of sexual and natural selection

Gonad size and shape asymmetries are particularly common in birds. Although some obvious size and shape differences between the left and right testes in birds were first documented more than a century ago, little is known about what influences the variation across species in either the degree or the direction of these asymmetries. Here we show that a left bias in size is the most likely ancestral state in most orders and families, and that there is a weak but significant negative relation between the degree of size and shape asymmetries. In extant species, testis size and shape symmetries increase with the degree of sperm competition (relative testes mass), but those relations are significant only in those species with left bias in each of these traits. When space is particularly constrained on the left side of the body cavity due to a large gizzard (e.g. in granivores), the left testis is more elongated and the degree of size symmetry is larger. Despite significant patterns, relative testes mass and gizzard complexity together explain < 10% of the variation in testis asymmetry in species with left biases. Thus our analyses suggest that some other factor is largely responsible for the evolution of gonad asymmetry in birds: 1) that a left bias in testis size might be a correlated response to selection for a left bias in the development of a single (left) ovary in females of most bird species, and/or 2) that physiological efficiency due to the dramatic and rapid increase in testis size of most species during the breeding season might favour enlargement of one testis. Our conclusions highlight the need to rethink and improve our understanding of the physiological processes underlying the investment in gonads by male birds.     

Demographic constraints in evolution: Towards unifying the evolutionary theories of senescence and niche conservatism

Summary I suggest that there may be a fundamental conceptual unity between two seemingly disparate phenomena: (1) senescence (the progressive deterioration in physiological function and, thus, individual fitness with age) and (2) niche conservatism (the observation that species often seem rather fixed over evolutionary time in their basic niche properties). I argue that both phenomena arise from demographic asymmetries. The evolutionary theory of ageing rests on the observation that the force of selection declines with age, reflecting the basic demographic facts that in persistent populations there are always fewer individuals in old than in young age classes and these individuals tend to have lower reproductive value. A similar demographic asymmetry arises when populations inhabit environments with source habitats (i.e. where conditions are within the species' niche) and sink habitats (where conditions lie outside the niche): there tend to be more individuals in sources than in sinks and individuals in sources have relatively higher reproductive values. These demographic asymmetries should often imply that the force of selection is greater in sources than in sinks, leading automatically towards niche conservatism. I suggest that niche evolution is most likely in circumstances where these demographic asymmetries in space weaken or reverse.     

Asymmetric regional cerebral blood flow in sedated baboons measured by positron emission tomography (PET)

The analysis of structural brain asymmetry has been a focal point in anthropological theories of human brain evolution and the development of lateralized behaviors. While physiological brain asymmetries have been documented for humans and animals presenting with pathological conditions or under certain activation tasks, published studies on baseline asymmetries in healthy individuals have produced conflicting results. We tested for the presence of cerebral blood flow asymmetries in 7 healthy, sedated baboons using positron emission tomography, a method of in vivo autoradiography. Five of the 7 baboons exhibited hemispheric asymmetries in which left-sided flow was significantly greater than right-sided flow. Furthermore, the degree of asymmetry in 8 of 24 brain regions was found to be significantly correlated with age; older individuals exhibited a higher degree of asymmetry than younger individuals. Cerebral blood flow itself was uncorrelated with age, and differences between males and females were not significant.     

Survival regression analysis: a powerful tool for evaluating fighting and assessment

Theoretical models of animal contests frequently generate predictions about how asymmetries (e.g. differences in size, residence status) between contestants affect fight duration. Linear regression and nonparametric correlation analyses are commonly used to test the fit of data to such models. We show how survival regression analysis (SRA) is a powerful technique for studying the effect of asymmetries on the duration of contests. SRA, which is under-utilized by students of animal behaviour, offers several advantages over more frequently used procedures. It provides unbiased parameter estimates even when including censored data (i.e. results of contests that have not ended at the time when observations are stopped). The analysis of hazard functions, which is a component of SRA, is an easy way to test for consistency with predictions of the sequential assessment game model. These and other advantages of SRA are illustrated by using SRA and more conventional methods to analyse the effect of asymmetries on contest duration for encounters between female Mediterranean tarantulas, Lycosa tarentula (L.). It is hoped that this example of the advantages of SRA will encourage more widespread use of this powerful technique. Copyright 2000 The Association for the Study of Animal Behaviour.     

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.     

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.     

Spatial guidance of cell asymmetry: septin GTPases show the way

Eukaryotic cells develop asymmetric shapes suited for specific physiological functions. Morphogenesis of polarized domains and structures requires the amplification of molecular asymmetries by scaffold proteins and regulatory feedback loops. Small monomeric GTPases signal polarity, but how their downstream effectors and targets are spatially co-ordinated to break cell symmetry is poorly understood. Septins comprise a novel family of GTPases that polymerize into non-polar filamentous structures which scaffold and restrict protein localization. Recent studies show that septins demarcate distinct plasma membrane domains and cytoskeletal tracks, enabling the formation of intracellular asymmetries. Here, we review these findings and discuss emerging mechanisms by which septins promote cell asymmetry in fungi and animals.     

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.     

A nonlinear model for transient responses from light-adapted wolf spider eyes

A quantitative model is proposed to test the hypothesis that the dynamics of nonlinearities in retinal action potentials from light-adapted wolf spider eyes may be due to delayed asymmetries in responses of the visual cells. For purposes of calculation, these delayed asymmetries are generated in an analogue by a time-variant resistance. It is first shown that for small incremental stimuli, the linear behavior of such a resistance describes peaking and low frequency phase lead in frequency responses of the eye to sinusoidal modulations of background illumination. It also describes the overshoots in linear step responses. It is next shown that the analogue accounts for nonlinear transient and short term DC responses to large positive and negative step stimuli and for the variations in these responses with changes in degree of light adaptation. Finally, a physiological model is proposed in which the delayed asymmetries in response are attributed to delayed rectification by the visual cell membrane. In this model, cascaded chemical reactions may serve to transduce visual stimuli into membrane resistance changes.     

Interplay between age‐based competitive asymmetries within the brood and direct competition between inbred and outbred offspring in a burying beetle

Theory suggests that intraspecific competition associated with direct competition between inbred and outbred individuals should be an important determinant of the severity of inbreeding depression. The reason is that, if outbred individuals are stronger competitors than inbred ones, direct competition should have a disproportionate effect on the fitness of inbred individuals. However, an individual's competitive ability is not only determined by its inbreeding status but also by competitive asymmetries that are independent of an individual's inbreeding status. When this is the case, such competitive asymmetries may shape the outcome of direct competition between inbred and outbred individuals. Here, we investigate the interface between age‐based competitive asymmetries within broods and direct competition between inbred and outbred offspring in the burying beetle Nicrophorus vespilloides. We found that inbred offspring had lower survival than outbred ones confirming that there was inbreeding depression. Furthermore, seniors (older larvae) grew to a larger size and had higher survival than juniors (younger larvae), confirming that there were age‐based competitive asymmetries. Nevertheless, there was no evidence that direct competition between inbred and outbred larvae exacerbated inbreeding depression, no evidence that inbreeding depression was more severe in juniors and no evidence that inbred juniors suffered disproportionately due to competition from outbred seniors. Our results suggest that direct competition between inbred and outbred individuals does not necessarily exacerbate inbreeding depression and that inbred individuals are not always more sensitive to poor and stressful conditions than outbred ones.     

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.     

Contest outcome in a territorial butterfly: the role of motivation

In many butterfly species, males compete over areas advantageous for encountering females. Rules for contest settlement are, however, largely unknown and neither morphological nor physiological traits can reliably predict the contest outcome. Here, we test the hypothesis that contests are settled in accordance with a motivation asymmetry. We staged contests between males of Pararge aegeria and after removing the resident, the non-resident was allowed (i) either to interact with a non-receptive female for 30 min (n = 30) or (ii) to spend 30 min alone in the cage (n = 30), after which the initial resident was reintroduced. The results show that males that had interacted with a female had a higher probability of becoming dominant and reversing contest outcome. Moreover, males that were faster to take over a vacant territory when the resident was removed were more likely to become dominant. Here, we show for the first time, to our knowledge, that frequent encounters with a mated female can increase male motivation to persist in a territorial contest in a butterfly. Further, we suggest that variation in intrinsic motivation reflects male eagerness to take over vacant territory. This study indicates that variation in resource value and motivational asymmetries are important for settling contests in butterflies.     

¿I like the way you move¿: how hormonal changes across the menstrual cycle affect female perceptions of gait

ABSTRACT: BACKGROUND: Variations in hormone concentrations across the menstrual cycle affect human female mate preferences. It has been shown that around the time of ovulation human females prefer more masculine male voices, faces, and bodies while simultaneously preferring less faces that are more feminine. They prefer also displays of male dominance, males with more symmetrical faces, and the scent of males with high levels of body symmetry. The aim of the experiments reported here was to investigate whether there are changes in female preferences for walking gaits across the menstrual cycle. RESULTS: Experiment 1 showed female observers could discriminate between point-light walkers with low and high levels of fluctuating asymmetries in their gaits. Female observers were more sensitive to asymmetries in female gaits than they were for asymmetries in male gaits. Experiment 2 showed that level of gait asymmetry did not affect the abilities of observers to discriminate female from male walkers. Experiment 3 showed that female observers did not change their preference for low and high asymmetry walkers across their menstrual cycles. However, females showed a decreased preference for all female walkers at the time during which it was estimated observers were at peak fertility. That same change in preference was not observed for male walkers. CONCLUSIONS: These data suggest female observers may not value gait asymmetry, as a mate selection cue, in the same way that they value asymmetries in faces and bodies. While only "average" gaits were used in these experiments, rather than the gaits of individual walkers, the types of asymmetries in gait tested here were not used in the same way as static cues for judging the apparent healthiness of individuals. Females do discriminate well average female gait asymmetries and do change their preferences for those gaits across their menstrual cycle. Doing so may reflect the operation of processes that equip females with an advantage when competing for mates at times of peak fertility.     

Biphasic finite element simulation of the TMJ disc from in vivo kinematic and geometric measurements

Understanding the biomechanical nature of the degeneration of the temporomandibular joint requires a coupling between experimental measurements and numerical simulation. In this study, geometry measured from MRI, and motion obtained from a specially designed optoelectronic system are fed into a three-dimensional biphasic finite element analysis to generate the spatial and temporal mechanical response of the disc. This study demonstrates how this coupling can effectively predict the biomechanical response of the temporomandibular joint disc to physiological loading. For small jaw opening movements, asymmetries in the load of the disc are found, with especially higher shear stresses in the lateral portion.     

The ecology of asymmetry in stickleback defense structures

Slight departures from bilateral symmetry are usually associated with reduced fitness. Here we show that an insular freshwater population of Gasterosteus aculeatus exhibits spatial and temporal segregation according to the incidence and direction of asymmetry in the number of bony lateral plates, which are important predator-defense structures. We analyzed 11,263 fish collected from 19 full lake transects over three years, and found that signed asymmetries for plate number were slightly left-side biased. Asymmetries occurred in 55% of the stickleback with more asymmetrics found during cold weather, and more left-biased individuals found during windy conditions, possibly due to environmentally driven activity levels that differ among asymmetric forms. Absolute plate asymmetries were randomly distributed in the lake, but there was a strong shift in signed plate asymmetry from a mean of zero in littoral zones to left-side bias in limnetic zones, probably due to microhabitat choices among asymmetric forms. Video data of avian piscivores on the lake show laterality in prey handling, providing a potential mechanism for asymmetric prey morphology. Our results imply a complex relationship between slight asymmetries and niche space that is relevant to the broader literature on the evolutionary implications of developmental instability and intrapopulation variability.     

Physical simulation of laryngeal disorders using a multiple-mass vocal fold model

This paper reports on the use of a high-dimensional discrete vocal fold model for the simulation of voice production under the presence of laryngeal disorders. Specifically, the effect of increases in mass and stiffness, both unilateral and bilateral, has been analysed independently for both magnitudes. The glottal flow waveform and the mass displacement have been studied and the obtained results are coherent with clinical observations that relate mass increments with lowered fundamental frequencies and mass and stiffness increments with reduced vibratory amplitudes of vocal folds. The reported results also indicate that asymmetries in the physical properties of vocal folds result in asymmetries in their vibratory patterns, including phase, amplitude and behaviour on collision. These are also correlated with voice perturbation measures such as jitter, shimmer and normalised noise energy.