Cell cycle-related changes in the surface properties of amoebae of the cellular slime mould Dictyostelium discoideum

AbstractAmoebae of the cellular slime mould Dictyostelium discoideum were harvested during exponential, axenic growth and were partitioned in a dextran-poly(ethylene glycol) two-phase system in a countercurrent distribution apparatus. Amoebae in G1-, S- and G2-phases of the cell cycle were located in different parts of the countercurrent distribution. Since partitioning separates cells with different surface properties, it is concluded that there are cell cycle-related changes in the surface properties, and thus plasma membrane structure, of the amoebae

Razumijevanje heterogenosti matičnih stanica – preduvjet za uspješnu (dentalnu) regeneraciju

Advancements in regenerative dentistry could soon equip dentists with tools to regenerate dental pulp and other tissues. Developing effective regenerative therapies has proven to be a challenging task due to the complexity of tooth structure, functional and aesthetic requirements, safety and patient factors. However, recent studies looking at behaviour of adult mesenchymal stem cells in murine teeth in vivo offer new insights for development of translational approaches for tissue regeneration. Molecular heterogeneity within the mesenchymal stem cell (MSC) niche has recently been studied in vivo using genetic lineage tracing and single-cell RNA sequencing. The role of an established, Thy1 (CD90)-marked sub-population is studied in homeostasis and following stimulation of increased growth of mouse incisors. Recent results suggest that this sub-population plays a specific role in rapid growth, during development as well as in stimulated increased growth and can be replenished by activation of dormant stem cells. These findings have implications for development of new, targeted regenerative therapies harnessing the potential of tissue-resident stem cells in a surgical intervention or non-surgical, molecular signal delivery approach.Napredak u regenerativnoj dentalnoj medicini uskoro bi mogao opskrbiti doktore dentalne medicine alatima za regeneraciju zubne pulpe i drugih tkiva. Razvoj djelotvornih regenerativnih terapija pokazao se izazovom zbog složenosti zubne strukture i funkcije, estetskih zahtjeva, sigurnosti primjene i faktora rizika pojedinačnih pacijenata. Ipak, nove studije koje prate ponašanje mezenhimskih stanica in vivo u zubima odraslih miševa nude nove spoznaje za razvoj translacijskih pristupa za regeneraciju tkiva. U zadnje vrijeme dolazi se do novih spoznaja o molekularnoj heterogenosti unutar niše mezenhimskih matičnih stanica koristeći genetsko praćenje stanićne loze in vivo i RNK sekvenciranjem pojedinačnih stanica. Uloga subpopulacije obilježene dobro poznatim biljegom Thy1 (CD90) proučavana je u homeostazi i nakon stimulacije ubrzanog rasta sjekutića. Posljednji rezultati sugeriraju da ova subpopulacija igra ulogu u fazama ubrzanog rasta, tijekom razvoja i nakon stimulacije rasta te da se može dodatno producirati aktivacijom stanica u fazi mirovanja. Ovi rezultati imaju implikacije za razvoj novih, ciljanih regenerativnih terapija koje bi koristile potencijal tkivnih matičnih stanica u kirurškoj intervenciji ili u nekirurškom pristupu primjenom molekularnih signala

Co-evolutionary patterning of teeth and taste buds

Teeth and taste buds are iteratively patterned structures that line the oro-pharynx of vertebrates. Biologists do not fully understand how teeth and taste buds develop from undifferentiated epithelium or how variation in organ density is regulated. These organs are typically studied independently because of their separate anatomical location in mammals: teeth on the jaw margin and taste buds on the tongue. However, in many aquatic animals like bony fishes, teeth and taste buds are colocalized one next to the other. Using genetic mapping in cichlid fishes, we identified shared loci controlling a positive correlation between tooth and taste bud densities. Genome intervals contained candidate genes expressed in tooth and taste bud fields. sfrp5 and bmper, notable for roles in Wingless (Wnt) and bone morphogenetic protein (BMP) signaling, were differentially expressed across cichlid species with divergent tooth and taste bud density, and were expressed in the development of both organs in mice. Synexpression analysis and chemical manipulation of Wnt, BMP, and Hedgehog (Hh) pathways suggest that a common cichlid oral lamina is competent to form teeth or taste buds. Wnt signaling couples tooth and taste bud density and BMP and Hh mediate distinct organ identity. Synthesizing data from fish and mouse, we suggest that the Wnt-BMP-Hh regulatory hierarchy that configures teeth and taste buds on mammalian jaws and tongues may be an evolutionary remnant inherited from ancestors wherein these organs were copatterned from common epithelium

Expression and regulation of the Msx1 natural antisense transcript during development

Bidirectional transcription, leading to the expression of an antisense (AS) RNA partially complementary to the protein coding sense (S) RNA, is an emerging subject in mammals and has been associated with various processes such as RNA interference, imprinting and transcription inhibition. Homeobox genes do not escape this bidirectional transcription, raising the possibility that such AS transcription occurs during embryonic development and may be involved in the complexity of regulation of homeobox gene expression. According to the importance of the Msx1 homeobox gene function in craniofacial development, especially in tooth development, the expression and regulation of its recently identified AS transcripts were investigated in vivo in mouse from E9.5 embryo to newborn, and compared with the S transcript and the encoded protein expression pattern and regulation. The spatial and temporal expression patterns of S, AS transcripts and protein are consistent with a role of AS RNA in the regulation of Msx1 expression in timely controlled developmental sites. Epithelial–mesenchymal interactions were shown to control the spatial organization of S and also AS RNA expression during early patterning of incisors and molars in the odontogenic mesenchyme. To conclude, this study clearly identifies the Msx1 AS RNA involvement during tooth development and evidences a new degree of complexity in craniofacial developmental biology: the implication of endogenous AS RNAs

Some Navigation Rules for D-Brane Monodromy

We explore some aspects of monodromies of D-branes in the Kahler moduli space of Calabi-Yau compactifications. Here a D-brane is viewed as an object of the derived category of coherent sheaves. We compute all the interesting monodromies in some nontrivial examples and link our work to recent results and conjectures concerning helices and mutations. We note some particular properties of the 0-brane.Comment: LaTeX2e, 28 pages, 4 figures, some typos corrected and refs adde

Lrp4 Modulates Extracellular Integration of Cell Signaling Pathways in Development

The extent to which cell signaling is integrated outside the cell is not currently appreciated. We show that a member of the low-density receptor-related protein family, Lrp4 modulates and integrates Bmp and canonical Wnt signalling during tooth morphogenesis by binding the secreted Bmp antagonist protein Wise. Mouse mutants of Lrp4 and Wise exhibit identical tooth phenotypes that include supernumerary incisors and molars, and fused molars. We propose that the Lrp4/Wise interaction acts as an extracellular integrator of epithelial-mesenchymal cell signaling. Wise, secreted from mesenchyme cells binds to BMP's and also to Lrp4 that is expressed on epithelial cells. This binding then results in the modulation of Wnt activity in the epithelial cells. Thus in this context Wise acts as an extracellular signaling molecule linking two signaling pathways. We further show that a downstream mediator of this integration is the Shh signaling pathway

The dystrotelin, dystrophin and dystrobrevin superfamily: new paralogues and old isoforms

BACKGROUND: Dystrophins and dystrobrevins are distantly related proteins with important but poorly understood roles in the function of metazoan muscular and neuronal tissues. Defects in them and their associated proteins cause a range of neuromuscular disorders. Members of this superfamily have been discovered in a relatively serendipitous way; we set out to compile a comprehensive description of dystrophin- and dystrobrevin-related sequences from available metazoan genome sequences, validated in representative organisms by RT-PCR, or acquired de novo from key species. RESULTS: Features of the superfamily revealed by our survey include: a) Dystrotelin, an entirely novel branch of the superfamily, present in most vertebrates examined. Dystrotelin is expressed in the central nervous system, and is a possible orthologue of Drosophila DAH. We describe the preliminary characterisation of its function, evolution and expression. b) A novel vertebrate member of the dystrobrevin family, γ-dystrobrevin, an ancient branch now extant only in fish, but probably present in our own ancestors. Like dystrophin, zebrafish γ-dystrobrevin mRNA is localised to myosepta. c) The extent of conservation of alternative splicing and alternative promoter use in the dystrophin and dystrobrevin genes; alternative splicing of dystrophin exons 73 and 78 and α-dystrobrevin exon 13 are conserved across vertebrates, as are the use of the Dp116, Dp71 and G-utrophin promoters; the Dp260 and Dp140 promoters are tetrapod innovations. d) The evolution of the unique N-terminus of DRP2 and its relationship to Dp116 and G-utrophin. e) A C-terminally truncated common ancestor of dystrophin and utrophin in cyclostomes. f) A severely restricted repertoire of dystrophin complex components in ascidians. CONCLUSION: We have refined our understanding of the evolutionary history and isoform diversity of the five previously reported vertebrate superfamily members and describe two novel members, dystrotelin and γ-dystrobrevin. Dystrotelins, dystrophins and dystrobrevins are roughly equally related to each other. Vertebrates therefore have a repertoire of seven superfamily members (three dystrophins, three dystrobevins, and one dystrotelin), with one lost in tetrapods. Most invertebrates studied have one member from each branch. Although the basic shared function which is implied by the common architecture of these distantly related proteins remains unclear, it clearly permeates metazoan biology