Two molecular models of initial left-right asymmetry generation

Left-right (LR) asymmetry is a fascinating problem in embryonic morphogenesis. Recently, a pathway of genes has been identified which is involved in LR patterning in vertebrates. Although this work characterizes the interactions of several asymmetrically-expressed genes, it is still entirely unclear how such asymmetric expression is set up in the first place. There are two promising molecular candidates which may play a role is such a process: the motor protein dynein, and the gap junction protein connexin-43 (Cx43). We present two models, significantly supported by previous findings, which hypothesize that (a) dynein asymmetrically localizes LR determinants in individual cells to establish cell-autonomous LR biasing, and (b) asymmetric activity of Cx43 gap junctions within key cells sets up electric potentials in multicellular fields, thus establishing large-scale LR asymmetry.     

Pitx2 participates in the late phase of the pathway controlling left-right asymmetry

BACKGROUND: We have studied the role of the different MHC (RT1) subregions in acute natural killer (NK) cell-mediated bone marrow allograft rejection in lethally irradiated, bone marrow cell (BMC) reconstituted rats. METHODS: We employed a series of MHC congenic and intra-MHC recombinant rat strains so that effects of mismatches in defined RT1 subregions could be studied systematically. BMC allograft survival was measured as 125IUdR uptake in the spleen between day 5 and day 7 after irradiation and BMC reconstitution. RESULTS: We found that in certain RT1 haplotype combinations, nonclassical RT1.C disparities by themselves could determine graft rejection (i.e., in the u/av1 recombinant haplotypes), whereas in another combination (between the av1 and c haplotypes) a mismatch for an isolated classical RT1.A region was decisive for engraftment. Thus, PVG.R1 BMC failed to proliferate in PVG rats, differing in the RT1.A region only, whereas in PVG.1U rats rejection could be determined by isolated differences in the RT1.C region (LEW.1WR1). Also, RT1 homozygous rats (RT1.U) rejected semi-allogeneic F1 hybrid BMC. The acute rejection of BMC was mediated by NK cells, as athymic nude rats, lacking alloreactive T cells but with normal alloreactive NK cells, showed the same patterns of rejection as did normal rats. Nude rats also rejected allogeneic lymphocytes, a previously documented NK-mediated phenomenon, with identical requirements of MHC disparity. CONCLUSIONS: This investigation shows that rat effector NK cells are radioresistant, independent of the thymus, and capable of recognizing and rejecting MHC mismatched transplanted BMC on the basis of mismatches in both classical and nonclassical class I regions in vivo. The studies underline the importance also of NK cells in determining BMC allograft survival.     

Control of vertebrate left-right asymmetry by a snail-related zinc finger gene

A gene encoding a zinc finger protein of the Snail family, cSnR, is expressed in the right-hand lateral mesoderm during normal chick development. Antisense disruption of cSnR function during the hours immediately preceding heart formation randomized the normally reliable direction of heart looping and subsequent embryo torsion. Implanted ectopic sources of intercellular signal proteins that are involved in establishing normal left-right information randomized the handedness of heart development and also altered the asymmetry of cSnR expression. cSnR thus appears to act downstream of these signals, or perhaps in parallel with the latest expressed of them, the Nodal protein, in controlling the anatomical asymmetry.     

Observational learning of a left-right behavioral asymmetry in mice (Mus musculus).

B6D2F? hybrid mice that were allowed to observe a trained female mouse open a pendulum door to the right (or to the left) to enter a food compartment later solved this problem faster than pupils that had been placed behind a visual barrier. Male pupils that had observed a "left-handed" teacher performed sinistrally; males that had observed a "right-handed" model performed dextrally. Female pupils did not exhibit their demonstrator's laterality. Observational learning may provide a means to maintain certain lateralized behaviors. Such social learning may lead to the emergence of local traditions and to the cultural diffusion of behavioral asymmetries. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential expression of flectin in the extracellular matrix and left-right asymmetry in mouse embryonic heart during looping stages

The characteristics of six different indicators of response distortion on the Personality Assessment Inventory (PAI; Morey, 1991) were evaluated by having college students complete the PAI under positive impression management, malingering, and honest responding conditions. The six indicators were the PAI Positive Impression (PIM) and Negative Impression (NIM) scales, the Malingering and Defensiveness Indexes, and two discriminant functions, one developed by Cashel and the other by Rogers. Protocols of students asked to malinger were compared with those of actual clinical patients, while protocols of students asked to manage their impression in a positive direction were compared with those of students asked to respond honestly. Comparisons between groups were accomplished through the examination of effect sizes and receiver operating characteristic (ROC) curves. All six indicators demonstrated the ability to distinguish between actual and feigned responding. The Rogers function was particularly effective in identifying malingering. The Cashel function was less effective than other measures in identifying positive impression management, although it appears to also have promise as an indicator of malingering.     

Functional differences among Xenopus nodal-related genes in left-right axis determination

An association has been noted previously in chick, mouse and frog embryos between asymmetric nodal-related gene expression and embryonic situs, implying an evolutionarily conserved role in left-right specification. Of the four Xenopus nodal-related genes expressed during gastrulation, only Xnr-1 is re-expressed unilaterally in the left lateral plate mesoderm at neurula/tailbud stages. Here, we show that the asymmetric expression of Xnr-1 can be made bilaterally symmetric by right-sided microinjection of RNA encoding active Xenopus hedgehog proteins. Moreover, we provide the first evidence that Xnr-1 expression per se is a causal factor in left-right axis determination. When plasmids expressing Xnr-1 were delivered unilaterally to the right side of Xenopus embryos, a reversed laterality of both the heart and gut (homotaxic reversal) was induced in 40% of surviving embryos, while an additional 10-20% showed reversal of the heart or gut alone (heterotaxia). This effect on laterality was specific to Xnr-1, since neither Xnr-2 nor Xnr-3 plasmids had this activity. In addition, we find that Xnr-1 and Xnr-2, which have both been defined as mesoderm inducers from overexpression studies, show quantitative differences in their ability to induce dorsal mesoderm. Together, these findings suggest that the various Xnrs perform substantially different functions during Xenopus embryogenesis. Moreover, they strongly support the hypothesis that left lateral plate expression of nodal-related genes is a causative factor in the determination of asymmetry in vertebrate embryos.     

The AEP T-complex to synthesised musical tones: left-right asymmetry in relation to handedness and hemisphere dominance

The Siberian hamster, Phodopus sungorus, breeds seasonally. In the laboratory, the seasonal breeding can be controlled by photoperiod, which affects the durations of nightly melatonin secretions. Winterlike short day lengths induce gonadal regression in adult animals, and pups born and maintained in short days undergo gonadal development much later than animals born into long days. The spinal nucleus of the bulbocavernosus (SNB) and its target muscles, the bulbocavernosus (BC) and levator ani (LA), comprise a sexually dimorphic, androgensensitive neuromuscular system involved in male reproduction. The SNB neuromuscular system was studied in male Siberian hamsters maintained from conception in short-day (8:16 h light/dark cycle) versus long-day (16:8 h light/dark cycle) conditions. At 40-47 days of age, development of three components of the SNB neuromuscular system were all significantly delayed in hamsters raised in the short photoperiod: BC/LA muscle weight, the size of SNB motoneuronal somata, and the area of the neuromuscular junctions at the BC/LA muscles of short-day hamsters were each significantly reduced relative to those of longday counterparts. Thus, development of the SNB reproductive system is delayed under short day lengths in this species.     

Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein

Microtubule-dependent motor, murine KIF3B, was disrupted by gene targeting. The null mutants did not survive beyond midgestation, exhibiting growth retardation, pericardial sac ballooning, and neural tube disorganization. Prominently, the left-right asymmetry was randomized in the heart loop and the direction of embryonic turning. lefty-2 expression was either bilateral or absent. Furthermore, the node lacked monocilia while the basal bodies were present. Immunocytochemistry revealed KIF3B localization in wild-type nodal cilia. Video microscopy showed that these cilia were motile and generated a leftward flow. These data suggest that KIF3B is essential for the left-right determination through intraciliary transportation of materials for ciliogenesis of motile primary cilia that could produce a gradient of putative morphogen along the left-right axis in the node.     

The left-right problem in psychology.

The first half of the paper makes some general observations on the difficulty of telling left from right. In particular, it is suggested that the problem of discriminating mirror-image stimuli, such as b and d, is not a problem of perception, but is rather one of remembering which label applies to which stimulus. The paper then discusses three different theories of left-right confusion, which share the common idea that coding is left-right reversed between the two halves of the brain. The theories proposed by Orton and by Noble are rejected in favour of a compromise theory which states that there is veridical exchange of perceptual information between the cerebral hemispheres, but that there is a left-right reversal in the transfer of memory traces from one hemisphere to the other. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context effects in left-right shape discrimination.

The difficulty of discriminating between left–right orientations of a shape has usually been attributed to symmetrical coding in the brain or to the nature of perceptual learning. However, recent work on the context-dependent nature of the difficulty challenges such explanations and supports a more cognitive approach to the problem. The present work examined the basis for left–right difficulty in the standard two-choice task (stimuli aligned side by side) in children of 3 to 4 years. Experiment 1 found that children who learned the task with the easy, single-stimulus procedure could generalize to the difficult, two-choice task. Subsequent experiments found that the difficulty in learning the two-choice task could not be attributed to the attentional demands of the two stimuli, nor to the use of the second stimulus as a spatial referent for defining orientation. The data suggested that the standard two-choice task is difficult because it promotes the use of two competing orientation judgments. We conclude that the difficulty of left–right judgments lies in the cognitive demands of the task and is to be understood in the same terms as other problems in cognitive development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular mechanisms of vertebrate left-right development

Patterning of all tissues and organs in the vertebrate embryo occurs along the dorsoventral (DV), anteroposterior (AP), and left-right (LR) body axes. Whereas significant progress has been made in identifying the processes underlying DV and AP patterning, relatively little is known about mechanisms guiding LR development. The significant incidence of human disease conditions associated with LR laterality defects, particularly those of the cardiovascular system, underscores the importance of understanding how LR asymmetries become established in the embryo. The focus of this review is on recently identified genes that are involved in generation of vertebrate LR asymmetry, and the proposed cellular and molecular mechanisms by which they might function in initiation, propagation and interpretation of LR patterning information.     

Neutrino masses and lepton-flavor-violating τ decays in the supersymmetric left-right model

In the supersymmetric left-right model, the light neutrino masses are given by the Type-seesaw mechanism. A duality property of this mechanism indicates that there exist eight possible Higgs triplet Yukawa couplings which result in the same neutrino mass     

Physical asymmetry of the crystallographic

The texture of a mill-produced, Nb-bearing, interstitial-free, hot-rolled sheet steel was evaluated at a number of sheet thickness positions. The texture was also studied following laboratory cold rolling and following recrystallization. A “nonsymmetric case” crystallite orientation distribution function analysis applicable to the analysis on nonsymmetric pole figures was used. While sheet steels are generally assumed to have orthotropic physical symmetry, it was found that an appreciable degree of physical asymmetry existed. The asymmetry was with respect to the rolling direction (RD) and normal direction (ND) mirror planes, while transverse direction (TD) mirror-plane symmetry existed.