Epigenetic events in mammalian germ-cell development: reprogramming and beyond

The epigenetic profile of germ cells, which is defined by modifications of DNA and chromatin, changes dynamically during their development. Many of the changes are associated with the acquisition of the capacity to support post-fertilization development. Our knowledge of this aspect has greatly increased- for example, insights into how the re-establishment of parental imprints is regulated. In addition, an emerging theme from recent studies is that epigenetic modifiers have key roles in germ-cell development itself--for example, epigenetics contributes to the gene-expression programme that is required for germ-cell development, regulation of meiosis and genomic integrity. Understanding epigenetic regulation in germ cells has implications for reproductive engineering technologies and human health.     

Roles of actin binding proteins in mammalian oocyte maturation and beyond

Actin nucleation factors, which promote the formation of new actin filaments, have emerged in the last decade as key regulatory factors controlling asymmetric division in mammalian oocytes. Actin nucleators such as formin-2, spire, and the ARP2/3 complex have been found to be important regulators of actin remodeling during oocyte maturation. Another class of actin-binding proteins including cofilin, tropomyosin, myosin motors, capping proteins, tropomodulin, and Ezrin-Radixin-Moesin proteins are thought to control actin cytoskeleton dynamics at various steps of oocyte maturation. In addition, actin dynamics controlling asymmetric-symmetric transitions after fertilization is a new area of investigation. Taken together, defining the mechanisms by which actin-binding proteins regulate actin cytoskeletons is crucial for understanding the basic biology of mammalian gamete formation and pre-implantation development.     

Male pregnancy in seahorses and pipefish: beyond the mammalian model

Pregnancy has been traditionally defined as the period during which developing embryos are incubated in the body after egg-sperm union. Despite strong similarities between viviparity in mammals and other vertebrate groups, researchers have historically been reluctant to use the term pregnancy for non-mammals in recognition of the highly developed form of viviparity in eutherians. Syngnathid fishes (seahorses and pipefishes) have a unique reproductive system, where the male incubates developing embryos in a specialized brooding structure in which they are aerated, osmoregulated, protected and likely provisioned during their development. Recent insights into physiological, morphological and genetic changes associated with syngnathid reproduction provide compelling evidence that male incubation in these species is a highly specialized form of reproduction akin to other forms of viviparity. Here, we review these recent advances, highlighting similarities and differences between seahorse and mammalian pregnancy. Understanding the changes associated with the parallel evolution of male pregnancy in the two major syngnathid lineages will help to identify key innovations that facilitated the development of this unique form of reproduction and, through comparison with other forms of live bearing, may allow the identification of a common set of characteristics shared by all viviparous organisms.     

MAM (mitochondria-associated membranes) in mammalian cells: Lipids and beyond

One mechanism by which communication between the endoplasmic reticulum (ER) and mitochondria is achieved is by close juxtaposition between these organelles via mitochondria-associated membranes (MAM). The MAM consist of a region of the ER that is enriched in several lipid biosynthetic enzyme activities and becomes reversibly tethered to mitochondria. Specific proteins are localized, sometimes transiently, in the MAM. Several of these proteins have been implicated in tethering the MAM to mitochondria. In mammalian cells, formation of these contact sites between MAM and mitochondria appears to be required for key cellular events including the transport of calcium from the ER to mitochondria, the import of phosphatidylserine into mitochondria from the ER for decarboxylation to phosphatidylethanolamine, the formation of autophagosomes, regulation of the morphology, dynamics and functions of mitochondria, and cell survival. This review focuses on the functions proposed for MAM in mediating these events in mammalian cells. In light of the apparent involvement of MAM in multiple fundamental cellular processes, recent studies indicate that impaired contact between MAM and mitochondria might underlie the pathology of several human neurodegenerative diseases, including Alzheimer's disease. Moreover, MAM has been implicated in modulating glucose homeostasis and insulin resistance, as well as in some viral infections.     

Lipooligosaccharide of Campylobacter jejuni: similarity with multiple types of mammalian glycans beyond gangliosides

Campylobacter jejuni is well known for synthesizing ganglioside mimics within the glycan component of its lipooligosaccharide (LOS), which have been implicated in triggering Guillain-Barré syndrome. We now confirm that this pathogen is capable of synthesizing a much broader spectrum of host glycolipid/glycoprotein mimics within its LOS. P blood group and paragloboside (lacto-N-neotetraose) antigen mimicry is exhibited by RM1221, a strain isolated from a poultry source. RM1503, a gastroenteritis-associated strain, expresses lacto-N-biose and sialyl-Lewis c units, the latter known as the pancreatic tumor-associated antigen, DU-PAN-2 (or LSTa). C. jejuni GC149, a Guillain-Barré syndrome-associated strain, expresses an unusual sialic acid-containing hybrid oligosaccharide with similarity to both ganglio and Pk antigens and can, through phase variation of its LOS biosynthesis genes, display GT1a or GD3 ganglioside mimics. We show that the sialyltransferase CstII and the galactosyltransferase CgtD are involved in the synthesis of multiple mimic types, with LOS structural diversity achieved through evolving allelic substrate specificity.     

Lipid-metabolizing serine hydrolases in the mammalian central nervous system: endocannabinoids and beyond

The metabolic serine hydrolases hydrolyze ester, amide, or thioester bonds found in broad small molecule substrates using a conserved activated serine nucleophile. The mammalian central nervous system (CNS) express a diverse repertoire of serine hydrolases that act as (phospho)lipases or lipid amidases to regulate lipid metabolism and signaling vital for normal neurocognitive function and CNS integrity. Advances in genomic DNA sequencing have provided evidence for the role of these lipid-metabolizing serine hydrolases in neurologic, psychiatric, and neurodegenerative disorders. This review briefly summarizes recent progress in understanding the biochemical and (patho)physiological roles of these lipid-metabolizing serine hydrolases in the mammalian CNS with a focus on serine hydrolases involved in the endocannabinoid system. The development and application of specific inhibitors for an individual serine hydrolase, if available, are also described.This article is part of a Special Issue entitled Novel functions of phospholipase A2 Guest Editors: Makoto Murakami and Gerard Lambeau.     

ComprehendingCornus: Puzzles and progress in the systematics of the dogwoods

Dogwoods evolved in two main lineages, a red-fruited line in which the inflorescences have basal bracts, and a blue-(or white-)fruited line in which the bracts are rudimentary or lacking. The 15 “red-line” species are mostly well marked, whereas “blue-line” species—numbering roughly 50 if some newer treatments be accepted—are mostly hard to tell apart. Red-line ovules are tenuinucellate, blue-line ovules crassinucellate. Dividing the red line separates cornelian cherries from the showy-bracted species; dividing the latter separates dwarf cornels from big-bracted dogwoods. Adding in the blue line there are thus four subgroups, which differ with regard to inflorescences— and with regard to iridoid glucosides, among other things. I downplay further subdivision (into opposite- and alternateleaved blue-line groups, for instance) and focus on few traits because I aim to trace the subgroups backward in the fossil record, to decide the direction of evolutionary changes, and to infer the causes for divergence. Unlike pollen, leaves, and wood, fossil dogwood fruits can often be assigned to one of the four subgroups and sometimes to a species group within a subgroup.Dunstania (based on fruits from England’s early Tertiary and here transferred toCornus’s cornelian cherry subgroup) or something close to the dunstanias gave rise to modernC. volkensii of Africa and four related species found today in California and Eurasia. Fossil fruit-stones of the blue line, like their modern counterparts, can be subglobose, compressed and asymmetric, fluted, or topped by a deep depression. Such a deep depression serves to link a fossil to the extant speciesC. alternifolia andC. controversa, but other features of the blue-line fruitstones, overlapping and less constant, cannot be used to prove a fossil’s tie to groups within the blue line. Evidence of several kinds makes the blue-line dogwoods oldest and connectsCornus to the nyssoids:Nyssa, Camptotheca, andDavidia. Commonly called Nyssaceae after 1910, when Wangerin got their traits wrong, the nyssoids are surer relatives ofCornus than any of Wangerin’s (“Das Pflanzenreich”) cornaceous genera.Mastixia, however, may be the actual sister group because it shares withCornus 1-celled 2-armed hairs that nyssoids lack.Cornus, nyssoids, and mastixioids (modernMastixia and its closest fossil allies) are here regarded as the true Cornaceae. Other genera once thought to be cornaceous are doubtfully to not at all related. As is now widely known, discordant features makeCorokia andKaliphora (for example) out of place in the Cornaceae, butAucuba andGarrya (for example) are neither easily excluded by a listing of their traits nor easily included by construction of branched diagrams. The novelty that brought about the radiation of true cornads was, I think, epigyny, followed fairly quickly by the hard endocarp and singleseeded locules. Mastixioid fruits of the late Cretaceous were dry or leathery and smaller than their successors. This suggests that early members of the family spread abiotically or by means of animals that ate whole plants. Bigger, fleshier fruits came later through interaction with evolving frugivores. The cause of early radiation withinCornus probably was interaction with insect predators and pollinators. One species of the blue line escaped competition for spring pollinators by switching to fall flowering and thereby kept some traits that other dogwoods lost. Though birds are now the main dispersers of the dogwoods, rodents likely play a minor role, and monkeys likely played a major role when compound fruits evolved. Though gynoecial reduction was the rule in dogwoods,C. (Dunstania) multilocularis’s multiple seed chambers reflect an evolutionary increase. I postulate that modernCornus’s 4-merous flower with 2-merous ovary has a strong developmental tie to pairing of the leaves and branches.     

Three-Dimensional Puzzles: Southern African and Upper Palaeolithic Rock Art

The history of anthropology is a growing field of study within the discipline itself. Our series 'Key Informants on the History of Anthropology' contributes to the discussion of how anthropology, as it is understood and practised today, evolved and took shape. In the following invited contribution, David Lewis-Williams reflects on the major reinterpretation of southern African rock art and Upper Palaeolithic art that took place in the 1970s and 1980s. An earlier interpretation of the rock art as representing hunters' impressions of their prey was replaced by sophisticated interpretations of the cosmology of the first inhabitants of South Africa. Lewis-Williams's work was crucial in bringing about this shift. David Lewis-Williams is Professor Emeritus of Archaeology and founder of the Rock Art Research Institute of the University of the Witwatersrand, South Africa, which promotes studies of the more than 15,000 sites within the country.