DUF1220-Domain Copy Number Implicated in Human Brain-Size Pathology and Evolution

DUF1220 domains show the largest human-lineage-specific increase in copy number of any protein-coding region in the human genome and map primarily to 1q21, where deletions and reciprocal duplications have been associated with microcephaly and macrocephaly, respectively. Given these findings and the high correlation between DUF1220 copy number and brain size across primate lineages (R² = 0.98; p = 1.8 × 10⁻⁶), DUF1220 sequences represent plausible candidates for underlying 1q21-associated brain-size pathologies. To investigate this possibility, we used specialized bioinformatics tools developed for scoring highly duplicated DUF1220 sequences to implement targeted 1q21 array comparative genomic hybridization on individuals (n = 42) with 1q21-associated microcephaly and macrocephaly. We show that of all the 1q21 genes examined (n = 53), DUF1220 copy number shows the strongest association with brain size among individuals with 1q21-associated microcephaly, particularly with respect to the three evolutionarily conserved DUF1220 clades CON1(p = 0.0079), CON2 (p = 0.0134), and CON3 (p = 0.0116). Interestingly, all 1q21 DUF1220-encoding genes belonging to the NBPF family show significant correlations with frontal-occipital-circumference Z scores in the deletion group. In a similar survey of a nondisease population, we show that DUF1220 copy number exhibits the strongest correlation with brain gray-matter volume (CON1, p = 0.0246; and CON2, p = 0.0334). Notably, only DUF1220 sequences are consistently significant in both disease and nondisease populations. Taken together, these data strongly implicate the loss of DUF1220 copy number in the etiology of 1q21-associated microcephaly and support the view that DUF1220 domains function as general effectors of evolutionary, pathological, and normal variation in brain size.     

Role of auxin in regulating Arabidopsis flower development

To elucidate the role of auxin in flower morphogenesis, its distribution patterns were studied during flower development in Arabidopsis thaliana (L.) Heynh. Expression of DR5::GUS was regarded to reflect sites of free auxin, while immunolocalization with auxin polyclonal antibodies visualized conjugated auxin distribution. The youngest flower bud was loaded with conjugated auxin. During development, the apparent concentration of free auxin increased in gradual patterns starting at the floral-organ tip. Anthers are major sites of high concentrations of free auxin that retard the development of neighboring floral organs in both the acropetal and basipetal directions. The IAA-producing anthers synchronize flower development by retarding petal development and nectary gland activity almost up to anthesis. Tapetum cells of young anthers contain free IAA which accumulates in pollen grains, suggesting that auxin promotes pollen-tube growth towards the ovules. High amounts of free auxin in the stigma induce a wide xylem fan immediately beneath it. After fertilization, the developing embryos and seeds show elevated concentrations of auxin, which establish their axial polarity. This developmental pattern of auxin production during floral-bud development suggests that young organs which produce high concentrations of free IAA inhibit or retard organ-primordium initiation and development at the shoot tip. Electronic Supplementary Material Supplementary material is available for this article at This paper is dedicated to Orna Aloni for continuous support and management over many years.     

Control over the morphology and segregation of Zebrafish germ cell granules during embryonic development

Background

The founding member of the EMAP-like protein family is the Echinoderm Microtubule-Associated Protein (EMAP), so-named for its abundance in sea urchin, starfish, and sand dollar eggs. The EMAP-like protein family has five members in mammals (EML1 through EML5) and only one in both Drosophila (ELP-1) and C. elegans (ELP-1). Biochemical studies of sea urchin EMAP and vertebrate EMLs implicate these proteins in the regulation of microtubule stability. So far, however, the physiological function of this protein family remains unknown.

Results

We examined the expression pattern of C. elegans ELP-1 by means of transgenic gene expression in living embryos and adults, and by immunolocalization with an ELP-1-specific antibody in fixed tissues. In embryos, ELP-1 is expressed in the hypodermis. In larvae and adults, ELP-1 is expressed in the body wall, spermatheca and vulval muscles, intestine, and hypodermal seam cells. In muscle, ELP-1 is associated with adhesion complexes near the cell surface and is bound to a criss-crossing network of microtubules in the cytoplasm. ELP-1 is also expressed in a subset of mechanoreceptor neurons, including the ray neurons in the male tail, microtubule-rich touch receptor neurons, and the six ciliated IL1 neurons. This restricted localization in the nervous system implies that ELP-1 plays a role in mechanotransmission. Consistent with this idea, decreasing ELP-1 expression decreases sensitivity to gentle touch applied to the body wall.

Conclusion

These data imply that ELP-1 may play an important role during the transmission of forces and signals between the body surface and both muscle cells and touch receptor neurons.     

Higher species richness of octocorals in the upper mesophotic zone in Eilat (Gulf of Aqaba) compared to shallower reef zones

Mesophotic coral-reef ecosystems (MCEs), which comprise the light-dependent communities of corals and other organisms found at depths between 30 and ~ 150 m, have received very little study to date. However, current technological advances, such as remotely operated vehicles and closed-circuit rebreather diving, now enable their thorough investigation. Following the reef-building stony corals, octocorals are the second most common benthic component on many shallow reefs and a major component on deep reefs, the Red Sea included. This study is the first to examine octocoral community features on upper MCEs based on species-level identification and to compare them with the shallower reef zones. The study was carried out at Eilat (Gulf of Aqaba, northern Red Sea), comparing octocoral communities at two mesophotic reefs (30–45 m) and two shallow reef zones (reef flat and upper fore-reef) by belt transects. A total of 30 octocoral species were identified, with higher species richness on the upper MCEs compared to the shallower reefs. Although the MCEs were found to host a higher number of species than the shallower reefs, both featured a similar diversity. Each reef zone revealed a unique octocoral species composition and distinct community structure, with only 16% of the species shared by both the MCEs and the shallower reefs. This study has revealed an almost exclusive dominance of zooxanthellate species at the studied upper MCE reefs, thus indicating an adequate light regime for photosynthesis there. The findings should encourage similar studies on other reefs, aimed at understanding the spatiotemporal features and ecological role of octocorals in reef ecosystems down to the deepest limit of the MCEs.     

Regulation of zebrafish primordial germ cell migration by attraction towards an intermediate target.

Migration of primordial germ cells (PGCs) from their site of specification towards the developing gonad is controlled by directional cues from somatic tissues. Although in several animals the PGCs are attracted by signals emanating from their final target, the gonadal mesoderm, little is known about the mechanisms that control earlier steps of migration. We provide evidence that a key step of zebrafish PGC migration, in which the PGCs become organized into bilateral clusters in the anterior trunk, is regulated by attraction of PGCs towards an intermediate target. Time-lapse observations of wild-type and mutant embryos reveal that bilateral clusters are formed at early somitogenesis, owing to migration of PGCs towards the clustering position from medial, posterior and anterior regions. Furthermore, PGCs migrate actively relative to their somatic neighbors and they do so as individual cells. Using mutants that exhibit defects in mesoderm development, we show that the ability to form PGC clusters depends on proper differentiation of the somatic cells present at the clustering position. Based on these findings, we propose that these somatic cells produce signals that attract PGCs. Interestingly, fate-mapping shows that these cells do not give rise to the somatic tissues of the gonad, but rather contribute to the formation of the pronephros. Thus, the putative PGC attraction center serves as an intermediate target for PGCs, which later actively migrate towards a more posterior position. This final step of PGC migration is defective in hands off mutants, where the intermediate mesoderm of the presumptive gonadal region is mispatterned. Our results indicate that zebrafish PGCs are guided by attraction towards two signaling centers, one of which may represent the somatic tissues of the gonad.     

Habitat selection in evolving mole rats

Summary The actively speciating four chromosomal species of fossorial mole rats of the Spalax ehrenbergi complex in Israel (2n=52, 58, 54 and 60) which inhabit an increasingly arid environment in this order were tested to determine their habitat preference. The testing apparatus simulated four climatic regimes based on temperature and humidity combinations corresponding to the climatic origins of the four chromosomal species: coolhumid, cool-dry, warm-humid and warm-dry, respectively. The tests involved 175 adults comprising all four chromosome species and representing 10 populations. Out of the 139 analyzed animals 88% selected the warm cages and only 12% selected the cool cages. The four karyotype progressively preferred the warm-dry cage in the following order: 53, 59, 60 and 72% for 2n=58, 52, 54 and 60 respectively, largely in accord with their increasingly arid climatic origins. Even larger differences were found in populations within karyotypes in accord with the local climatic variation within a karyotype range.The results of our analysis indicate that the chromosomal species and populations select their climatic habitat in accord with the climatic conditions of their geographic localities. The humidity index appears to be the prime differentiator of habitat selection and may have been a substantial ecological factor in species differentiation and distribution of the Spalax ehrenbergi complex in Israel.     

Primordial germ cell migration in the chick and mouse embryo: the role of the chemokine SDF-1/CXCL12

As in many other animals, the primordial germ cells (PGCs) in avian and reptile embryos are specified in positions distinct from the positions where they differentiate into sperm and egg. Unlike in other organism however, in these embryos, the PGCs use the vascular system as a vehicle to transport them to the region of the gonad where they exit the blood vessels and reach their target. To determine the molecular mechanisms governing PGC migration in these species, we have investigated the role of the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) in guiding the cells towards their target in the chick embryo. We show that sdf-1 mRNA is expressed in locations where PGCs are found and towards which they migrate at the time they leave the blood vessels. Ectopically expressed chicken SDF-1alpha led to accumulation of PGCs at those positions. This analysis, as well as analysis of gene expression and PGC behavior in the mouse embryo, suggest that in both organisms, SDF-1 functions during the second phase of PGC migration, and not at earlier phases. These findings suggest that SDF-1 is required for the PGCs to execute the final migration steps as they transmigrate through the blood vessel endothelium of the chick or the gut epithelium of the mouse.