Notch1 and T-cell development: insights from conditional knockout mice.

Notch proteins influence cell-fate decisions in many developmental systems. Gain-of-function studies have suggested a crucial role for Notch1 signaling at several stages during lymphocyte development, including the B/T, alphabeta/gammadelta and CD4/CD8 lineage choices. Here, we critically re-evaluate these conclusions in the light of recent studies that describe inducible and tissue-specific targeting of the Notch1 gene.

Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models.

A large fraction of genome variation between individuals is comprised of submicroscopic copy number variation of genomic DNA segments. We assessed the relative contribution of structural changes and gene dosage alterations on phenotypic outcomes with mouse models of Smith-Magenis and Potocki-Lupski syndromes. We phenotyped mice with 1n (Deletion/+), 2n (+/+), 3n (Duplication/+), and balanced 2n compound heterozygous (Deletion/Duplication) copies of the same region. Parallel to the observations made in humans, such variation in gene copy number was sufficient to generate phenotypic consequences: in a number of cases diametrically opposing phenotypes were associated with gain versus loss of gene content. Surprisingly, some neurobehavioral traits were not rescued by restoration of the normal gene copy number. Transcriptome profiling showed that a highly significant propensity of transcriptional changes map to the engineered interval in the five assessed tissues. A statistically significant overrepresentation of the genes mapping to the entire length of the engineered chromosome was also found in the top-ranked differentially expressed genes in the mice containing rearranged chromosomes, regardless of the nature of the rearrangement, an observation robust across different cell lineages of the central nervous system. Our data indicate that a structural change at a given position of the human genome may affect not only locus and adjacent gene expression but also "genome regulation." Furthermore, structural change can cause the same perturbation in particular pathways regardless of gene dosage. Thus, the presence of a genomic structural change, as well as gene dosage imbalance, contributes to the ultimate phenotype.

RNA-based gene duplication: mechanistic and evolutionary insights.

Gene copies that stem from the mRNAs of parental source genes have long been viewed as evolutionary dead-ends with little biological relevance. Here we review a range of recent studies that have unveiled a significant number of functional retroposed gene copies in both mammalian and some non-mammalian genomes. These studies have not only revealed previously unknown mechanisms for the emergence of new genes and their functions but have also provided fascinating general insights into molecular and evolutionary processes that have shaped genomes. For example, analyses of chromosomal gene movement patterns via RNA-based gene duplication have shed fresh light on the evolutionary origin and biology of our sex chromosomes.

Most and Least Preferred Colours Differ According to Object Context : New Insights from an Unrestricted Colour Range

Humans like some colours and dislike others, but which particular colours and why remains to be understood. Empirical studies on colour preferences generally targeted most preferred colours, but rarely least preferred (disliked) colours. In addition, findings are often based on general colour preferences leaving open the question whether results generalise to specific objects. Here, 88 participants selected the colours they preferred most and least for three context conditions (general, interior walls, t-shirt) using a high-precision colour picker. Participants also indicated whether they associated their colour choice to a valenced object or concept. The chosen colours varied widely between individuals and contexts and so did the reasons for their choices. Consistent patterns also emerged, as most preferred colours in general were more chromatic, while for walls they were lighter and for t-shirts they were darker and less chromatic compared to least preferred colours. This meant that general colour preferences could not explain object specific colour preferences. Measures of the selection process further revealed that, compared to most preferred colours, least preferred colours were chosen more quickly and were less often linked to valenced objects or concepts. The high intra- and inter-individual variability in this and previous reports furthers our understanding that colour preferences are determined by subjective experiences and that most and least preferred colours are not processed equally.