Neuropilin asymmetry mediates a left-right difference in habenular connectivity

The medial habenular nuclei of the zebrafish diencephalon, which lie bilateral to the pineal complex, exhibit left-right differences in their neuroanatomy, gene expression profiles and axonal projections to the unpaired midbrain target--the interpeduncular nucleus (IPN). Efferents from the left habenula terminate along the entire dorsoventral extent of the IPN, whereas axons from the right habenula project only to the ventral IPN. How this left-right difference in connectivity is established and the factors involved in differential target recognition are unknown. Prior to IPN innervation, we find that only the left habenula expresses the zebrafish homologue of Neuropilin1a (Nrp1a), a receptor for class III Semaphorins (Sema3s). Directional asymmetry of nrp1a expression relies on Nodal signaling and the presence of the left-sided parapineal organ. Loss of Nrp1a, through parapineal ablation or depletion by antisense morpholinos, prevents left habenular neurons from projecting to the dorsal IPN. Selective depletion of Sema3D, but not of other Sema family members, similarly disrupts innervation of the dorsal IPN. Conversely, Sema3D overexpression results in left habenular projections that extend to the dorsal IPN, as well as beyond the target. The results indicate that Sema3D acts in concert with Nrp1a to guide neurons on the left side of the brain to innervate the target nucleus differently than those on the right side.     

Evolutionary role of phenotypic plasticity

Phenotypic plasticity, i.e., the ability of a genotype to produce various phenotypes in response to changes in the environment, plays an important, although poorly understood and often underestimated, role in evolution. Both adaptive and nonadaptive phenotypic plasticity modulate the strength and direction of selection acting on a population and can, depending on conditions, either accelerate or inhibit adaptation, divergence, and speciation. Phenotypic plasticity also affects the direction of evolutionary change, which can either coincide with the direction of plastic changes (genetic assimilation) or be the opposite (genetic compensation). A special case of phenotypic plasticity is phenotypic change of the host caused by changes in its symbiotic microbiota. In the current review, we discuss the main forms of phenotypic plasticity and the current data on their impact on the rate and direction of evolutionary change. Special attention is paid to the results of recent experimental work, including the long-term evolutionary experiment on Drosophila melanogaster, which is being held at the Department of Evolutionary Biology, School of Biology, Moscow State University.     

Sex-dependent structural asymmetry of the medial habenular nucleus of the chicken brain

Summary An investigation of structural asymmetry in the avian brain was conducted on the epithalamic medial habenular nucleus of the chicken. Twelve male and ten female two-day-old chickens were used for a morphometric evaluation of asymmetry. The medial habenular nucleus was measured from paraffin-wax-embedded, 8 m-thick sections by use of a semiautomatic image analyser. The volumes of the right and left medial habenula of each animal were statistically analysed (within animal experimental design). The right medial habenula in males showed significant group asymmetry. In contrast, females failed to demonstrate group bias in favour of either hemisphere. However, individual females were lateralised, with either a larger right or left medial habenula. Although individuals of both sexes were lateralised, there was no significant sex difference in volume in either the right or left medial habenula.We propose that sex-linked structural asymmetry may be influenced by steroid hormonal effects in the central nervous system, and that such asymmetry could be more prevalent in the non-mammalian vertebrate brain than previously considered.     

Selective asymmetry in a conserved forebrain to midbrain projection

How the left and right sides of the brain acquire anatomical and functional specializations is not well understood. The zebrafish has proven to be a useful model to explore the genetic basis of neuroanatomical asymmetry in the developing forebrain. The dorsal diencephalon or epithalamus consists of the asymmetric pineal complex and adjacent paired nuclei, the left and right medial habenulae, which in zebrafish larvae, exhibit differences in their size, neuropil density and patterns of gene expression. In all vertebrates, axons from the medial habenular nuclei project within a prominent fiber bundle, the fasciculus retroflexus, to a shared midbrain target, the interpeduncular nucleus of the ventral tegmentum. However, in zebrafish, projections from the left habenula innervate the dorsal and ventral regions of the target nucleus, whereas right habenular efferents project only to the ventral region. A similar dorsoventral difference in habenular connectivity is found in another teleost species, the highly derived southern flounder, Paralichthys lethostima. In this flatfish, directional asymmetry of the habenular projection appears to be independent of the left-right morphology and orientation that an individual adopts post-metamorphosis. Comparative anterograde labeling of the brains of salamanders, frogs and mice reveals that axons emanating from the left and right medial habenulae do not project to different domains, but rather, they traverse the target nucleus in a complementary mirror image pattern. Thus, although the habenulo-interpeduncular conduction system is highly conserved in the vertebrate brain, the stereotypic dorsoventral topography of left-right connections appears to be a feature that is specific to teleosts.     

Geometry and structural plasticity of synaptic connectivity

Changes in synaptic connectivity patterns through the formation and elimination of dendritic spines may contribute to structural plasticity in the brain. We characterize this contribution quantitatively by estimating the number of different synaptic connectivity patterns attainable without major arbor remodeling. This number depends on the ratio of the synapses on a dendrite to the axons that pass within a spine length of that dendrite. We call this ratio the filling fraction and calculate it from geometrical analysis and anatomical data. The filling fraction is 0.26 in mouse neocortex, 0.22-0.34 in rat hippocampus. In the macaque visual cortex, the filling fraction increases by a factor of 1.6-1.8 from area V1 to areas V2, V4, and 7a. Since the filling fraction is much smaller than 1, spine remodeling can make a large contribution to structural plasticity.     

Evolutionary plasticity of IL-6 cytokine family

The IL-6 family of cytokines includes a variety of proteins that function not only within the immune system, but also in other organs, tissues, and types of cells, including neurons. The common evolutionary origin of the IL-6 family proteins determines similar mechanisms of reception and intracellular signaling, although their primary structures are highly variable, as well as their biological functions. We have demonstrated that the members of the IL-6 family have high evolutionary plasticity. This manifests in a high degree of population polymorphism for IL-6 family genes, as well as varying degrees of evolutionary conservation among members of the family. The degree of evolutionary conservation of IL-6 family proteins does not correlate with the mechanisms of interaction between these cytokines and their receptors.     

Spatiotemporal asymmetry of associative synaptic plasticity in fear conditioning pathways

Input-specific long-term potentiation (LTP) in afferent inputs to the amygdala serves an essential function in the acquisition of fear memory. Factors underlying input specificity of synaptic modifications implicated in information transfer in fear conditioning pathways remain unclear. Here we show that the strength of naive synapses in two auditory inputs converging on a single neuron in the lateral nucleus of the amygdala (LA) is only modified when a postsynaptic action potential closely follows a synaptic response. The stronger inhibitory drive in thalamic pathway, as compared with cortical input, hampers the induction of LTP at thalamo-amygdala synapses, contributing to the spatial specificity of LTP in convergent inputs. These results indicate that spike timing-dependent synaptic plasticity in afferent projections to the LA is both temporarily and spatially asymmetric, thus providing a mechanism for the conditioned stimulus discrimination during fear behavior.     

Evolutionary reduction of developmental plasticity in desert spadefoot toads

Organisms vary their rates of growth and development in response to environmental inputs. Such developmental plasticity may be adaptive and positively correlate with environmental heterogeneity. However, the evolution of developmental plasticity among closely related taxa is not well understood. To determine the evolutionary pattern of plasticity, we compared plasticity in time to and size at metamorphosis in response to water desiccation in tadpoles among spadefoot species that differ in breeding pond and larval period durations. Like most tadpoles, spadefoot tadpoles possess the remarkable ability to accelerate development in response to pond drying to avoid desiccation. Here, we hypothesize that desert spadefoot tadpoles have evolved reduced plasticity to avoid desiccation in ephemeral desert pools compared to their nondesert relatives that breed in long-duration ponds. We recorded time to and size at metamorphosis following experimental manipulation of water levels and found that desert-adapted species had much less plasticity in larval period and size at metamorphosis than nondesert species, which retain the hypothetical ancestral state of plasticity. Furthermore, we observed a correlation between degree of plasticity and fat body content that may provide mechanistic insights into the evolution of developmental plasticity in amphibians.     

细胞色素P450介导抗性的进化可塑性

细胞色素P450是超基因家族,由其介导的杀虫剂代谢解毒的增强是昆虫产生抗药性的普遍而主要的机制。近年的研究表明,细胞色素P450介导的代谢抗性表现出一定程度的进化可塑性:即使是同种昆虫的不同种群在相同种类杀虫剂的胁迫下,进化选择出的抗性相关的细胞色素P450也有所不同,抗性的产生也可以是几种不同细胞色素P450协同作用或控制P450表达的调控因子的不同。     

Hemispheric asymmetry in white matter connectivity of the temporoparietal junction with the insula and prefrontal cortex

The temporoparietal junction (TPJ) is a key node in the brain's ventral attention network (VAN) that is involved in spatial awareness and detection of salient sensory stimuli, including pain. The anatomical basis of this network's right-lateralized organization is poorly understood. Here we used diffusion-weighted MRI and probabilistic tractography to compare the strength of white matter connections emanating from the right versus left TPJ to target regions in both hemispheres. Symmetry of structural connectivity was evaluated for connections between TPJ and target regions that are key cortical nodes in the right VAN (insula and inferior frontal gyrus) as well as target regions that are involved in salience and/or pain (putamen, cingulate cortex, thalamus). We found a rightward asymmetry in connectivity strength between the TPJ and insula in healthy human subjects who were scanned with two different sets of diffusion-weighted MRI acquisition parameters. This rightward asymmetry in TPJ-insula connectivity was stronger in females than in males. There was also a leftward asymmetry in connectivity strength between the TPJ and inferior frontal gyrus, consistent with previously described lateralization of language pathways. The rightward lateralization of the pathway between the TPJ and insula supports previous findings on the roles of these regions in stimulus-driven attention, sensory awareness, interoception and pain. The findings also have implications for our understanding of acute and chronic pains and stroke-induced spatial hemineglect.     

Evolutionary conserved role of ptf1a in the specification of exocrine pancreatic fates

We have characterized and mapped the zebrafish ptf1a gene, analyzed its embryonic expression, and studied its role in pancreas development. In situ hybridization experiments show that from the 12-somite stage to 48 hpf, ptf1a is dynamically expressed in the spinal cord, hindbrain, cerebellum, retina, and pancreas of zebrafish embryos. Within the endoderm, ptf1a is initially expressed at 32 hpf in the ventral portion of the pdx1 expression domain; ptf1a is expressed in a subset of cells located on the left side of the embryo posteriorly to the liver primordium and anteriorly to the endocrine islet that arises from the posterodorsal pancreatic anlage. Then the ptf1a expression domain buds giving rise to the anteroventral pancreatic anlage that grows posteriorly to eventually engulf the endocrine islet. By 72 hpf, ptf1a continues to be expressed in the exocrine compartment derived from the anteroventral anlage. Morpholino-induced ptf1a loss of function suppresses the expression of the exocrine markers, while the endocrine markers in the islet are unaffected. In mind bomb (mib) mutants, in which delta-mediated notch signalling is defective [Dev. Cell 4 (2003) 67], ptf1a is normally expressed. In addition, the slow-muscle-omitted (smu) mutants that lack expression of endocrine markers because of a defective hedgehog signalling [Curr. Biol. 11(2001) 1358] exhibit normal levels of ptf1a. This indicates that hedgehog signaling plays a different genetic role in the specification of the anteroventral (mostly exocrine) and posterodorsal (endocrine) pancreatic anlagen.     

Evolutionary placement of Xanthomonadales based on conserved protein signature sequences

Xanthomonadales comprises one of the largest phytopathogenic bacterial groups, and is currently classified within the gamma-proteobacteria. However, the phylogenetic placement of this group is not clearly resolved, and the results of different studies contradict one another. In this work, the evolutionary position of Xanthomonadales was determined by analyzing the presence of shared insertions and deletions (INDELs) in highly conserved proteins. Several distinctive insertions found in most of the members of the gamma-proteobacteria are absent in Xanthomonadales and groups such as Legionelalles, Chromatiales, Methylococcales, Thiotrichales and Cardiobacteriales. These INDELs were most likely introduced after the branching of Xanthomonadales from most of the gamma-proteobacteria and provide evidence for the phylogenetic placement of the early gamma-proteobacteria. Moreover, other proteins contain insertions exclusive to the Xanthomonadales order, confirming that this is a monophyletic group and provide important specific genetic markers. Thus, the data presented clearly support the Xanthomonadales group as an independent subdivision, and constitute one of the deepest branching lineage within the gamma-proteobacteria clade.     

Evolutionary growth process of highly conserved sequences in vertebrate genomes

Genome sequence comparison between evolutionarily distant species revealed ultraconserved elements (UCEs) among mammals under strong purifying selection. Most of them were also conserved among vertebrates. Because they tend to be located in the flanking regions of developmental genes, they would have fundamental roles in creating vertebrate body plans. However, the evolutionary origin and selection mechanism of these UCEs remain unclear. Here we report that UCEs arose in primitive vertebrates, and gradually grew in vertebrate evolution. We searched for UCEs in two teleost fishes, Tetraodon nigroviridis and Oryzias latipes, and found 554 UCEs with 100% identity over 100 bps. Comparison of teleost and mammalian UCEs revealed 43 pairs of common, jawed-vertebrate UCEs (jUCE) with high sequence identities, ranging from 83.1% to 99.2%. Ten of them retain lower similarities to the Petromyzon marinus genome, and the substitution rates of four non-exonic jUCEs were reduced after the teleost-mammal divergence, suggesting that robust conservation had been acquired in the jawed vertebrate lineage. Our results indicate that prototypical UCEs originated before the divergence of jawed and jawless vertebrates and have been frozen as perfect conserved sequences in the jawed vertebrate lineage. In addition, our comparative sequence analyses of UCEs and neighboring regions resulted in a discovery of lineage-specific conserved sequences. They were added progressively to prototypical UCEs, suggesting step-wise acquisition of novel regulatory roles. Our results indicate that conserved non-coding elements (CNEs) consist of blocks with distinct evolutionary history, each having been frozen since different evolutionary era along the vertebrate lineage.     

Evolutionary consequences of gender plasticity in genetically dimorphic breeding systems

A functional view of gender helps evolutionary biologists evaluate the mechanisms underlying breeding-system evolution. Evolutionary pathways from hermaphroditism to dioecy include the intermediate breeding systems of gynodioecy and androdioecy. These pathways start with the invasion of unisexual mutants, females or males, respectively, followed by alteration of the hermaphrodites to allocate more to the sexual function that the unisexuals lack. Eventually, hermaphrodites become unisexual and dioecy has evolved. Some species evolving along these pathways stop short of completing this second step, or even revert back from dioecy. We evaluate the hypothesis that gender plasticity is involved in these transitions to and from dioecy. Evidence from studies of subdioecious species that have evolved along the gynodioecy pathway suggests that gender plasticity occurs and stabilizes subdioecy by lowering the cost of producing seed. Factors influencing species evolving toward androdioecy, or reverting to androdioecy from dioecy, appear to be more varied and include reproductive assurance, herbivory and gender plasticity. In general, gender specialization appears to be favored in resource-poor environments regardless of which pathway is taken to dioecy.     

Cleavage pattern and emerging asymmetry of the mouse embryo

Early mammalian development is regulative - it is flexible and responsive to experimental intervention. This flexibility could be explained if embryogenesis were originally completely unbiased and disordered; order and determination of cells only arising later. Alternatively, regulative behaviour could be consistent with the embryo having some order or bias from the very beginning, with inflexibility and cell determination increasing steadily over time. Recent evidence supports the second view and indicates that the sequence and the orientations of cell divisions help to build the first asymmetries.