Targeting Mechanisms in Myelinated Axons: Not All Nodes Are Created Equal

A recent Neuron paper by Zhang et al. (2012) reveals how ion channels and adhesion molecules essential for rapid nerve conduction in vertebrates are differentially targeted to nodes of Ranvier. Moreover, distinct mechanisms regulate initial clustering and maintenance of specific nodal components

Putting the glue in glia: Necls mediate Schwann cell–axon adhesion

Interactions between Schwann cells and axons are critical for the development and function of myelinated axons. Two recent studies (see Maurel et al. on p. 861 of this issue; Spiegel et al., 2007) report that the nectin-like (Necl) proteins Necl-1 and -4 are internodal adhesion molecules that are critical for myelination. These studies suggest that Necl proteins mediate a specific interaction between Schwann cells and axons that allows proper communication of the signals that trigger myelination

Rapid Mapping of Zebrafish Mutations With SNPs and Oligonucleotide Microarrays

Large-scale genetic screens in zebrafish have identified thousands of mutations in hundreds of essential genes. The genetic mapping of these mutations is necessary to link DNA sequences to the gene functions defined by mutant phenotypes.Here, we report two advances that will accelerate the mapping of zebrafish mutations: (1) The construction of a first generation single nucleotide polymorphism (SNP) map of the zebrafish genome comprising 2035 SNPs and 178 small insertions/deletions, and (2) the development of a method for mapping mutations in which hundreds of SNPs can be scored in parallel with an oligonucleotide microarray.We have demonstrated the utility of the microarray technique in crosses with haploid and diploid embryos by mapping two known mutations to their previously identified locations.We have also used this approach to localize four previously unmapped mutations.We expect that mapping with SNPs and oligonucleotide microarrays will accelerate the molecular analysis of zebrafish mutations

Zebrafish Comparative Genomics and the Origins of Vertebrate Chromosomes

To help understand mechanisms of vertebrate genome evolution, we have compared zebrafish and tetrapod gene maps. It has been suggested that translocations are fixed more frequently than inversions in mammals. Gene maps showed that blocks of conserved syntenies between zebrafish and humans were large, but gene orders were frequently inverted and transposed. This shows that intrachromosomal rearrangements have been fixed more frequently than translocations. Duplicated chromosome segments suggest that a genome duplication occurred in ray-fin phylogeny, and comparative studies suggest that this event happened deep in the ancestry of teleost fish. Consideration of duplicate chromosome segments shows that at least 20% of duplicated gene pairs may be retained from this event. Despite genome duplication, zebrafish and humans have about the same number of chromosomes, and zebrafish chromosomes are mosaically orthologous to several human chromosomes. Is this because of an excess of chromosome fissions in the human lineage or an excess of chromosome fusions in the zebrafish lineage? Comparative analysis suggests that an excess of chromosome fissions in the tetrapod lineage may account for chromosome numbers and provides histories for several human chromosomes

Genetic Interactions in Zebrafish Midline Development

AbstractMutational analyses have shown that the genesno tail(ntl, Brachyuryhomolog),floating head(flh,aNothomeobox gene), andcyclops(cyc) play direct and essential roles in the development of midline structures in the zebrafish. In bothntlandflhmutants a notochord does not develop, and incycmutants the floor plate is nearly entirely missing. We made double mutants to learn how these genes might interact. Midline development is disrupted to a greater extent incyc;flhdouble mutants than in eithercycorflhsingle mutants; their effects appear additive. Both the notochord and floor plate are completely lacking, and other phenotypic disturbances suggest that midline signaling functions are severely reduced. On the other hand, trunk midline defects inflh;ntldouble mutants are not additive, but are most often similar to those inntlsingle mutants. This finding reveals that loss ofntlfunction can suppress phenotypic defects due to mutation atflh,and we interpret it to mean that the wild-type allele ofntl(ntl+) functions upstream toflhin a regulatory hierarchy. Loss of function ofntlalso strongly suppresses the floor plate deficiency incycmutants, for we found trunk floor plate to be present incyc;ntldouble mutants. From these findings we propose thatntl+plays an early role in cell fate choice at the dorsal midline, mediated by the Ntl protein acting to antagonize floor plate development as well as to promote notochord development

The Use of Genetics for the Management of a Recovering Population: Temporal Assessment of Migratory Peregrine Falcons in North America

Background: Our ability to monitor populations or species that were once threatened or endangered and in the process of recovery is enhanced by using genetic methods to assess overall population stability and size over time. This can be accomplished most directly by obtaining genetic measures from temporally-spaced samples that reflect the overall stability of the population as given by changes in genetic diversity levels (allelic richness and heterozygosity), degree of population differentiation (FST and DEST), and effective population size (Ne). The primary goal of any recovery effort is to produce a longterm self-sustaining population, and these genetic measures provide a metric by which we can gauge our progress and help make important management decisions. Methodology/Principal Findings: The peregrine falcon in North America (Falco peregrinus tundrius and anatum) was delisted in 1994 and 1999, respectively, and its abundance will be monitored by the species Recovery Team every three years until 2015. Although the United States Fish and Wildlife Service makes a distinction between tundrius and anatum subspecies, our genetic results based on eleven microsatellite loci suggest limited differentiation that can be attributed to an isolation by distance relationship and warrant no delineation of these two subspecies in its northern latitudinal distribution from Alaska through Canada into Greenland. Using temporal samples collected at Padre Island, Texas during migration (seven temporal time periods between 1985–2007), no significant differences in genetic diversity or significant population differentiation in allele frequencies between time periods were observed and were indistinguishable from those obtained from tundrius/anatum breeding locations throughout their northern distribution. Estimates of harmonic mean Ne were variable and imprecise, but always greater than 500 when employing multiple temporal genetic methods. Conclusions/Significance: These results, including those from simulations to assess the power of each method to estimate Ne, suggest a stable or growing population, which is consistent with ongoing field-based monitoring surveys. Therefore, historic and continuing efforts to prevent the extinction of the peregrine falcon in North America appear successful with no indication of recent decline, at least from the northern latitude range-wide perspective. The results also further highlight the importance of archiving samples and their use for continual assessment of population recovery and long-term viability

Carboxylic acids in clouds at a high-elevation forested site in central Virginia

During September 1990 we sampled coarse (>18-μm diameter) and fine (18- to 5.5-μm diameter) droplets and liquid-water content (LWC) in cloud from a tower on a forested ridge top in Shenandoah National Park, Virginia. Cloud-water pH and aqueous- and vapor-phase concentrations of carboxylic acids (HCOOH and CH3COOH) and formaldehyde (HCHO) were measured in parallel over 1- to 1.5-hour intervals. Both size fractions of cloud droplets contained similar concentrations of carboxylic species and H+ during most sampling; most cloud water was in coarse droplets. The pH of coarse (3.27–4.76) and fine (3.22–4.70) droplets coupled with total LWC of 0.04–0.56 g m−3 STP (standard m3 at 0°C and 1 atm) resulted in the partitioning of carboxylic acids primarily in the vapor phase. The observed phase partitioning for CH3COOH was within the uncertainty range of thermodynamic data. However, HCOOH exhibited significant phase disequilibria, which could not be explained by artifacts from variable LWC or from mixing droplets of different acidities. We hypothesize that the large volume of liquid water deposited on the forest canopy interacted with the near-surface cloud leading to apparent disequilibria based on time-integrated samples. HCOOH was selectively depleted relative to CH3COOH in cloud, particularly at higher pH, suggesting rapid removal of HCOOH by cloud-water deposition. We saw no evidence for significant production of HCOOH from the aqueous-phase oxidation of HCHO.Engineering and Applied Science

Carboxylic acids in the rural continental atmosphere over the eastern United States during the Shenandoah Cloud and Photochemistry Experiment

The Shenandoah Cloud and Photochemistry Experiment (SCAPE) was conducted during September 1990 in the rural continental atmosphere at a mountain top site (1014 m) in Shenandoah National Park, Virginia. We report here the extensive set of trace gas measurements performed during clear sky periods of SCAPE, with particular focus on the carboxylic acids, formic, acetic, and pyruvic. Median mixing ratios were 5.4 and 2.1 parts per billion by volume (ppbv) for formic and acetic acid, respectively, and they did not exhibit the diurnal variation characteristic of low-elevation sites. Mixing ratios of formic acid often approached or exceeded 10 ppbv, which are the largest values yet reported for the nonurban troposphere. Over the rural eastern United States, formic and acetic acid appear to have significant nonphotochemical sources. Secondary production from suspected pathways appears to be relatively unimportant. The observed lack of correlation between formic and acetic acid with peroxide species argues against a significant source from permutation reactions of peroxy radicals. In addition, model calculations using the SCAPE data indicate minimal production of carboxylics from olefin/O3 oxidation reactions. The tight correlation (r2 = 0.88) between mixing ratios of formic and acetic acid is strongly suggestive of a commonality in their sources. The seasonal cycle of carboxylic acids in the atmosphere and precipitation over the eastern United States is evidence that combustion emissions are not a principal source of these species. It appears that direct biogenic emissions from vegetation and soils cannot be ruled out as important sources. In particular, the correlation between the seasonal variation of formic and acetic acid and the ambient temperature is consistent with a soil microbial source. Similar conclusions were reached for pyruvic acid, with its mixing ratio ranging 4–266 parts per trillion by volume (pptv) (median = 63) and most likely supported by biogenic emissions and possibly photochemical sources.Engineering and Applied Science

Individual Neuronal Subtypes Exhibit Diversity in CNS Myelination Mediated by Synaptic Vesicle Release

SummaryRegulation of myelination by oligodendrocytes in the CNS has important consequences for higher-order nervous system function (e.g., [1–4]), and there is growing consensus that neuronal activity regulates CNS myelination (e.g., [5–9]) through local axon-oligodendrocyte synaptic-vesicle-release-mediated signaling [10–12]. Recent analyses have indicated that myelination along axons of distinct neuronal subtypes can differ [13, 14], but it is not known whether regulation of myelination by activity is common to all neuronal subtypes or only some. This limits insight into how specific neurons regulate their own conduction. Here, we use a novel fluorescent fusion protein reporter to study myelination along the axons of distinct neuronal subtypes over time in zebrafish. We find that the axons of reticulospinal and commissural primary ascending (CoPA) neurons are among the first myelinated in the zebrafish CNS. To investigate how activity regulates myelination by different neuronal subtypes, we express tetanus toxin (TeNT) in individual reticulospinal or CoPA neurons to prevent synaptic vesicle release. We find that the axons of individual tetanus toxin expressing reticulospinal neurons have fewer myelin sheaths than controls and that their myelin sheaths are 50% shorter than controls. In stark contrast, myelination along tetanus-toxin-expressing CoPA neuron axons is entirely normal. These results indicate that while some neuronal subtypes modulate myelination by synaptic vesicle release to a striking degree in vivo, others do not. These data have implications for our understanding of how different neurons regulate myelination and thus their own function within specific neuronal circuits