VEGF signals induce trailblazer cell identity that drives neural crest migration

Embryonic neural crest cells travel in discrete streams to precise locations throughout the head and body. We previously showed that cranial neural crest cells respond chemotactically to vascular endothelial growth factor (VEGF) and that cells within the migratory front have distinct behaviors and gene expression. We proposed a cell-induced gradient model in which lead neural crest cells read out directional information from a chemoattractant profile and instruct trailers to follow. In this study, we show that migrating chick neural crest cells do not display distinct lead and trailer gene expression profiles in culture. However, exposure to VEGF in vitro results in the upregulation of a small subset of genes associated with an in vivo lead cell signature. Timed addition and removal of VEGF in culture reveals the changes in neural crest cell gene expression are rapid. A computational model incorporating an integrate-and-switch mechanism between cellular phenotypes predicts migration efficiency is influenced by the timescale of cell behavior switching. To test the model hypothesis that neural crest cellular phenotypes respond to changes in the VEGF chemoattractant profile, we presented ectopic sources of VEGF to the trailer neural crest cell subpopulation and show diverted cell trajectories and stream alterations consistent with model predictions. Gene profiling of trailer cells that diverted and encountered VEGF revealed upregulation of a subset of ‘lead’ genes. Injection of neuropilin1 (Np1)-Fc into the trailer subpopulation or electroporation of VEGF morpholino to reduce VEGF signaling failed to alter trailer neural crest cell trajectories, suggesting trailers do not require VEGF to maintain coordinated migration. These results indicate that VEGF is one of the signals that establishes lead cell identity and its chemoattractant profile is critical to neural crest cell migration

Simulated Warming Differentially Affects the Growth and Competitive Ability of Centaurea maculosa Populations from Home and Introduced Ranges

Climate warming may drive invasions by exotic plants, thereby raising concerns over the risks of invasive plants. However, little is known about how climate warming influences the growth and competitive ability of exotic plants from their home and introduced ranges. We conducted a common garden experiment with an invasive plant Centaurea maculosa and a native plant Poa pratensis, in which a mixture of sand and vermiculite was used as a neutral medium, and contrasted the total biomass, competitive effects, and competitive responses of C. maculosa populations from Europe (home range) and North America (introduced range) under two different temperatures. The warming-induced inhibitory effects on the growth of C. maculosa alone were stronger in Europe than in North America. The competitive ability of C. maculosa plants from North America was greater than that of plants from Europe under the ambient condition whereas this competitive ability followed the opposite direction under the warming condition, suggesting that warming may enable European C. maculosa to be more invasive. Across two continents, warming treatment increased the competitive advantage instead of the growth advantage of C. maculosa, suggesting that climate warming may facilitate C. maculosa invasions through altering competitive outcomes between C. maculosa and its neighbors. Additionally, the growth response of C. maculosa to warming could predict its ability to avoid being suppressed by its neighbors

Cannabis-Dependence Risk Relates to Synergism between Neuroticism and Proenkephalin SNPs Associated with Amygdala Gene Expression: Case-Control Study

BACKGROUND:Many young people experiment with cannabis, yet only a subgroup progress to dependence suggesting individual differences that could relate to factors such as genetics and behavioral traits. Dopamine receptor D2 (DRD2) and proenkephalin (PENK) genes have been implicated in animal studies with cannabis exposure. Whether polymorphisms of these genes are associated with cannabis dependence and related behavioral traits is unknown. METHODOLOGY/PRINCIPAL FINDINGS:Healthy young adults (18-27 years) with cannabis dependence and without a dependence diagnosis were studied (N = 50/group) in relation to a priori-determined single nucleotide polymorphisms (SNPs) of the DRD2 and PENK genes. Negative affect, Impulsive Risk Taking and Neuroticism-Anxiety temperamental traits, positive and negative reward-learning performance and stop-signal reaction times were examined. The findings replicated the known association between the rs6277 DRD2 SNP and decisions associated with negative reinforcement outcomes. Moreover, PENK variants (rs2576573 and rs2609997) significantly related to Neuroticism and cannabis dependence. Cigarette smoking is common in cannabis users, but it was not associated to PENK SNPs as also validated in another cohort (N = 247 smokers, N = 312 non-smokers). Neuroticism mediated (15.3%-19.5%) the genetic risk to cannabis dependence and interacted with risk SNPs, resulting in a 9-fold increase risk for cannabis dependence. Molecular characterization of the postmortem human brain in a different population revealed an association between PENK SNPs and PENK mRNA expression in the central amygdala nucleus emphasizing the functional relevance of the SNPs in a brain region strongly linked to negative affect. CONCLUSIONS/SIGNIFICANCE:Overall, the findings suggest an important role for Neuroticism as an endophenotype linking PENK polymorphisms to cannabis-dependence vulnerability synergistically amplifying the apparent genetic risk

Invasive Plants and Enemy Release: Evolution of Trait Means and Trait Correlations in Ulex europaeus

Several hypotheses that attempt to explain invasive processes are based on the fact that plants have been introduced without their natural enemies. Among them, the EICA (Evolution of Increased Competitive Ability) hypothesis is the most influential. It states that, due to enemy release, exotic plants evolve a shift in resource allocation from defence to reproduction or growth. In the native range of the invasive species Ulex europaeus, traits involved in reproduction and growth have been shown to be highly variable and genetically correlated. Thus, in order to explore the joint evolution of life history traits and susceptibility to seed predation in this species, we investigated changes in both trait means and trait correlations. To do so, we compared plants from native and invaded regions grown in a common garden. According to the expectations of the EICA hypothesis, we observed an increase in seedling height. However, there was little change in other trait means. By contrast, correlations exhibited a clear pattern: the correlations between life history traits and infestation rate by seed predators were always weaker in the invaded range than in the native range. In U. europaeus, the role of enemy release in shaping life history traits thus appeared to imply trait correlations rather than trait means. In the invaded regions studied, the correlations involving infestation rates and key life history traits such as flowering phenology, growth and pod density were reduced, enabling more independent evolution of these key traits and potentially facilitating local adaptation to a wide range of environments. These results led us to hypothesise that a relaxation of genetic correlations may be implied in the expansion of invasive species