Hox genes: Downstream “effectors” of retinoic acid signaling in vertebrate embryogenesis

One of the major regulatory challenges of animal development is to precisely coordinate in space and time the formation, specification, and patterning of cells that underlie elaboration of the basic body plan. How does the vertebrate plan for the nervous and hematopoietic systems, heart, limbs, digestive, and reproductive organs derive from seemingly similar population of cells? These systems are initially established and patterned along the anteroposterior axis (AP) by opposing signaling gradients that lead to the activation of gene regulatory networks involved in axial specification, including the Hox genes. The retinoid signaling pathway is one of the key signaling gradients coupled to the establishment of axial patterning. The nested domains of Hox gene expression, which provide a combinatorial code for axial patterning, arise in part through a differential response to retinoic acid (RA) diffusing from anabolic centers established within the embryo during development. Hence, Hox genes are important direct effectors of retinoid signaling in embryogenesis. This review focuses on describing current knowledge on the complex mechanisms and regulatory processes, which govern the response of Hox genes to RA in several tissue contexts including the nervous system during vertebrate development.     

Adaptation to Host-Specific Bacterial Pathogens Drives Rapid Evolution of a Human Innate Immune Receptor

1. Download high-res image (261KB)
2. Download full-size image

     

Early emergence increases survival of tree seedlings in Central European temperate forests despite severe late frost

Global warming is expected to result in earlier emergence of tree seedlings that may experience higher damages and mortality due to late frost in spring. We monitored emergence, characteristics, and survival of seedlings across ten tree species in temperate mixed deciduous forests of Central Europe over one and a half year. We tested whether the timing of emergence represents a trade‐off for seedling survival between minimizing frost risk and maximizing the length of the growing period. Almost two‐thirds of the seedlings died during the first growing period. The timing of emergence was decisive for seedling survival. Although seedlings that emerged early faced a severe late frost event, they benefited from a longer growing period resulting in increased overall survival. Larger seedling height and higher number of leaves positively influenced survival. Seedlings growing on moss had higher survival compared to mineral soil, litter, or herbaceous vegetation. Synthesis. Our findings demonstrate the importance of emergence time for survival of tree seedlings, with early‐emerging seedlings more likely surviving the first growing period.     

Scale-up from shake flasks to fermenters in batch and continuous mode with Corynebacterium glutamicum on lactic acid based on oxygen transfer and pH

Scale-up from shake flasks to fermenters has been hampered by the lack of knowledge concerning the influence of operating conditions on mass transfer, hydromechanics, and power input. However, in recent years the properties of shake flasks have been described with empirical models. A practical scale-up strategy for everyday use is introduced for the scale-up of aerobic cultures from shake flasks to fermenters in batch and continuous mode. The strategy is based on empirical correlations of the volumetric mass transfer coefficient (k(L) a) and the pH. The accuracy of the empirical k(L) a correlations and the assumptions required to use these correlations for an arbitrary biological medium are discussed. To determine the optimal pH of the culture medium a simple laboratory method based on titration curves of the medium and a mechanistic pH model, which is solely based on the medium composition, is applied. The effectiveness of the scale-up strategy is demonstrated by comparing the behavior of Corynebacterium glutamicum on lactic acid in shake flasks and fermenters in batch and continuous mode. The maximum growth rate (micro(max) = 0.32 h(-1)) and the oxygen substrate coefficient (Y O2 /S= 0.0174 mol/l) of C. glutamicum on lactic acid were equal for shake flask, fermenter, batch, and continuous cultures. The biomass substrate yield was independent of the scale, but was lower in batch cultures (Y(X/S) = 0.36 g/g) than in continuous cultures (Y(X/S) = 0.45 g/g). The experimental data (biomass, respiration, pH) could be described with a simple biological model combined with a mechanistic pH model.     

Linking increasing drought stress to Scots pine mortality and bark beetle infestations

In the dry Swiss Rhone Valley, Scots pine forests have experienced increased mortality in recent years. It has commonly been assumed that drought events and bark beetles fostered the decline, however, whether bark beetle outbreaks increased in recent years and whether they can be linked to drought stress or increasing temperature has never been studied. In our study, we correlated time series of drought indices from long-term climate stations, 11-year mortality trends from a long-term research plot, and mortality probabilities modeled from tree rings (as an indicator of tree vitality) with documented occurrences of various bark beetle species and a buprestid beetle, using regional Forest Service reports from 1902 to 2003 and advisory cases of the Swiss Forest Protection Service (SFPS) from 1984 to 2005. We compared the historical findings with measured beetle emergence from a 4-year tree felling and breeding chamber experiment. The documented beetle-related pine mortality cases increased dramatically in the 1990s, both in the forest reports and the advisory cases. The incidents of beetle-related pine mortality correlated positively with spring and summer temperature, and with the tree-ring based mortality index, but not with the drought index. The number of advisory cases, on the other hand, correlated slightly with summer drought index and temperature, but very highly with tree-ring-based mortality index. The tree-ring-based mortality index and observed tree mortality increased in years following drought. This was confirmed by the beetle emergences from felled trees. Following dry summers, more than twice as many trees were colonized by beetles than following wet summers. We conclude that increased temperatures in the Swiss Rhone Valley have likely weakened Scots pines and favored phloeophagous beetle population growth. Beetles contributed to the increased pine mortality following summer drought. Among the factors not addressed in this study, changed forest use may have also contributed to increased beetle populations and Scots pine mortality, whereas air pollution seems to be of lesser importance.     

Rapidly reversible chlorophyll fluorescence quenching induced by pulses of supersaturating light in vivo

The saturation pulse method provides a means to distinguish between photochemical and non-photochemical quenching, based on the assumption that the former is suppressed by a saturating pulse of light (SP) and that the latter is not affected by the SP. Various types of non-photochemical quenching have been distinguished by their rates of dark relaxation in the time ranges of seconds, minutes, and hours. Here we report on a special type of non-photochemical quenching, which is rapidly induced by a pulse of high-intensity light, when PS II reaction centers are closed, and rapidly relaxes again after the pulse. This high-intensity quenching, HIQ, can be quantified by pulse-amplitude-modulation (PAM) fluorimetry (MULTI-COLOR-PAM, high sensitivity combined with high time resolution) via the quasi-instantaneous post-pulse fluorescence increase that precedes recovery of photochemical quenching in the 100–400-µs range. The HIQ amplitude increases linearly with the effective rate of quantum absorption by photosystem II, reaching about 8% of maximal fluorescence yield. It is not affected by DCMU, is stimulated by anoxic conditions, and is suppressed by energy-dependent non-photochemical quenching (NPQ). The HIQ amplitude is close to proportional to the square of maximal fluorescence yield, Fm′, induced by an SP and varied by NPQ. These properties are in line with the working hypothesis of HIQ being caused by the annihilation of singlet excited chlorophyll a by triplet excited carotenoid. Significant underestimation of maximal fluorescence yield and photosystem II quantum yield in dark-acclimated samples can be avoided by use of moderate SP intensities. In physiologically healthy illuminated samples, NPQ prevents significant lowering of effective photosystem II quantum yield by HIQ, if excessive SP intensities are avoided.

     

Uncoupling the BMP receptor antagonist function from the WNT agonist function of R-spondin 2 using the inhibitory peptide dendrimer RWd

Signaling by bone morphogenetic proteins (BMPs) plays pivotal roles in embryogenesis, adult tissue homeostasis, and disease. Recent studies revealed that the well-established WNT agonist R-spondin 2 (RSPO2) is also a BMP receptor (BMP receptor type 1A) antagonist, with roles in early Xenopus embryogenesis and human acute myeloid leukemia (AML). To uncouple the BMP antagonist function from the WNT agonist function and to promote development of AML therapeutics, here we identified a 10-mer peptide (RW) derived from the thrombospondin 1 domain of RSPO2, which specifically prevents binding between RSPO2 and BMP receptor type 1A without altering WNT signaling. We also show that a corresponding RW dendrimer (RW^d) exhibiting improved half-life relieves inhibition of BMP receptor signaling by RSPO2 in human AML cells, reduces cell growth, and induces differentiation. Moreover, microinjection of RW^d in Xenopus embryos ventralizes the dorsoventral embryonic patterning by upregulating BMP signaling without affecting WNT signaling. Our study corroborates the function of RSPO2 as a BMP receptor antagonist and provides a proof of concept for pharmacologically uncoupling BMP antagonist from WNT agonist functions of RSPO2 using the inhibitor peptide RW^d with enhanced target selectivity and limited side effects.     

DNA mini‐barcodes in taxonomic assignment: a morphologically unique new homoneurous moth clade from the Indian Himalayas described in Micropterix (Lepidoptera,Micropterigidae)

Lees, D. C., Rougerie, R., Zeller‐Lukashort, C. & Kristensen, N. P. (2010). DNA mini‐barcodes in taxonomic assignment: a morphologically unique new homoneurous moth clade from the Indian Himalayas described in Micropterix (Lepidoptera, Micropterigidae). —Zoologica Scripta, 39, 642–661. The first micropterigid moths recorded from the Himalayas, Micropterix cornuella sp. n. and Micropterix longicornuella sp. n. (collected, respectively, in 1935 in the Arunachel Pradesh Province and in 1874 in Darjeeling, both Northeastern India) constitute a new clade, which is unique within the family because of striking specializations of the female postabdomen: tergum VIII ventral plate forming a continuous sclerotized ring, segment IX bearing a pair of strongly sclerotized lateroventral plates, each with a prominent horn‐like posterior process. Fore wing vein R unforked, all Rs veins preapical; hind wing devoid of a discrete vein R. The combination of the two first‐mentioned vein characters suggests close affinity to the large Palearctic genus Micropterix (to some species of which the members of the new clade bear strong superficial resemblance). Whilst absence of the hind wing R is unknown in that genus, this specialization is not incompatible with the new clade being subordinate within it. A 136‐bp fragment of Cytochrome oxidase I successfully amplified from both of the 75‐year‐old specimens strongly supports this generic assignment. Translated to amino acids, this DNA fragment is highly diagnostic of this genus, being identical to that of most (16 of the 26) Micropterix species studied comparatively here, 1–4 codons different from nine other species (including Micropterix wockei that in phylogenetic analyses we infer to be sister to other examined species), whilst 7–15 codons different to other amphiesmenopteran genera examined here. A dating analysis also suggests that the large clade excluding M. wockei to which M. cornuella belongs appeared <31 million years ago. These findings encourage discovery of a significant radiation of Micropterix in the Himalayan region. Our analysis has more general implications for testing the assignment of DNA mini‐barcodes to a taxon, in cases such as museum specimens where the full DNA barcode cannot be recovered.     

Nicalin and its binding partner Nomo are novel Nodal signaling antagonists

Nodals are signaling factors of the transforming growth factor-beta (TGFbeta) superfamily with a key role in vertebrate development. They control a variety of cell fate decisions required for the establishment of the embryonic body plan. We have identified two highly conserved transmembrane proteins, Nicalin and Nomo (Nodal modulator, previously known as pM5), as novel antagonists of Nodal signaling. Nicalin is distantly related to Nicastrin, a component of the Alzheimer's disease-associated gamma-secretase, and forms a complex with Nomo. Ectopic expression of both proteins in zebrafish embryos causes cyclopia, a phenotype that can arise from a defect in mesendoderm patterning mediated by the Nodal signaling pathway. Accordingly, downregulation of Nomo resulted in an increase in anterior axial mesendoderm and the development of an enlarged hatching gland. Inhibition of Nodal signaling by ectopic expression of Lefty was rescued by reducing Nomo levels. Furthermore, Nodal- as well as Activin-induced signaling was inhibited by Nicalin and Nomo in a cell-based reporter assay. Our data demonstrate that the Nicalin/Nomo complex antagonizes Nodal signaling during mesendodermal patterning in zebrafish.