Of fingers, toes and penises

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62765/1/390029a0.pd

Purinergic signalling-evoked intracellular Ca(2+) concentration changes in the regulation of chondrogenesis and skeletal muscle formation.

It is now widely recognised that changes of the intracellular calcium concentration have deep impact on the differentiation of various non-excitable cells including the elements of the vertebrate skeleton. It has become evident that purinergic signalling is one of the most ancient cellular mechanisms that can cause such alterations in the intracellular Ca(2+)-homeostasis, which are precisely set either spatially or temporally. Purinergic signalling is believed to regulate intracellular Ca(2+)-concentration of developing cartilage and skeletal muscle cells and suggested to play roles in the modulation of various cellular functions. This idea is supported by the fact that pluripotent mesenchymal cells, chondroprogenitors or muscle precursors, as well as mature chondrocytes all are capable of releasing ectonucleotides, and express various types of purinoreceptors and ectonucleotidases. The presence of the basic components of purinergic signalling proves that cells of the chondrogenic lineage can utilise this mechanism for modulating their intracellular Ca(2+) concentration independently from the surrounding skeletal muscle and bone tissues, which are well known to release ectopurines during development and mechanical stress. In this review, we summarize accumulating experimental evidence supporting the importance of purinergic signalling in the regulation of chondrogenesis and during skeletal muscle formation

Deletion of a HoxD enhancer induces transcriptional heterochrony leading to transposition of the sacrum.

A phylogenetically conserved transcriptional enhancer necessary for the activation of Hoxd-11 was deleted from the HoxD complex of mice by targeted mutagenesis. While genetic and expression analyses demonstrated the role of this regulatory element in the activation of Hoxd-11 during early somitogenesis, the function of this gene in developing limbs and the urogenital system was not affected, suggesting that Hox transcriptional controls are different in different axial structures. In the trunk of mutant embryos, transcriptional activation of Hoxd-11 and Hoxd-10 was severely delayed, but subsequently resumed with appropriate spatial distributions. The resulting caudal transposition of the sacrum indicates that proper vertebral specification requires a precise temporal control of Hox gene expression, in addition to spatial regulation. A slight time delay in expression (transcriptional heterochrony) cannot be compensated for at a later developmental stage, eventually leading to morphological alterations

Large scale transgenic and cluster deletion analysis of the HoxD complex separate an ancestral regulatory module from evolutionary innovations.

The ancestral role of the Hox gene family is specifying morphogenetic differences along the main body axis. In vertebrates, HoxD genes were also co-opted along with the emergence of novel structures such as limbs and genitalia. We propose that these functional recruitments relied on the appearance, or implementation, of regulatory sequences outside of the complex. Whereas transgenic human and murine HOXD clusters could function during axial patterning, in mice they were not expressed outside the trunk. Accordingly, deletion of the entire cluster abolished axial expression, whereas recently acquired regulatory controls were preserved

Engineering chromosomes in mice through targeted meiotic recombination (TAMERE)

Functional studies of large transcription units, clustered genes and chromosomal loci require the design of novel experimental tools to engineer genomic macro-rearrangements. Here, we present a strategy to produce deficiencies or duplications by crossing mice carrying loxP sites in homologous loci. This trans -allelic targeted meiotic recombination (TAMERE) protocol allows for the combination of various alleles within a particular locus as well as for generation of interchromosomal unequal exchanges. Novel genetic configurations can thus be produced without multiple targeting and selection steps in embryonic stem (ES) cells. A concomitant deletion/duplication event of the Hoxd12 locus shows the potential of this approach. The high frequency of such targeted exchanges in vivo makes TAMERE a powerful genetic tool applicable to research areas in which complex genomic modifications are required.</p

A latent capacity for evolutionary innovation through exaptation in metabolic systems

Some evolutionary innovations may originate non-adaptively as exaptations, or pre-adaptations, which are by-products of other adaptive traits. Examples include feathers, which originated before they were used in flight, and lens crystallins, which are light-refracting proteins that originated as enzymes. The question of how often adaptive traits have non-adaptive origins has profound implications for evolutionary biology, but is difficult to address systematically. Here we consider this issue in metabolism, one of the most ancient biological systems that is central to all life. We analyse a metabolic trait of great adaptive importance: the ability of a metabolic reaction network to synthesize all biomass from a single source of carbon and energy. We use novel computational methods to sample randomly many metabolic networks that can sustain life on any given carbon source but contain an otherwise random set of known biochemical reactions. We show that when we require such networks to be viable on one particular carbon source, they are typically also viable on multiple other carbon sources that were not targets of selection. For example, viability on glucose may entail viability on up to 44 other sole carbon sources. Any one adaptation in these metabolic systems typically entails multiple potential exaptations. Metabolic systems thus contain a latent potential for evolutionary innovations with non-adaptive origins. Our observations suggest that many more metabolic traits may have non-adaptive origins than is appreciated at present. They also challenge our ability to distinguish adaptive from non-adaptive traits