The Future of Cell Biology: Emerging Model Organisms

Most current research in cell biology uses just a handful of model systems including yeast, Arabidopsis, Drosophila, Caenorhabditis elegans, zebrafish, mouse, and cultured mammalian cells. And for good reason - for many biological questions, the best system for the question is likely to be found among these models. However, in some cases, and particularly as the questions that engage scientists broaden, the best system for a question may be a little-studied organism. Modern research tools are facilitating a renaissance for unusual and interesting organisms as emerging model systems. As a result, we predict that an ever-expanding breadth of model systems may be a hallmark of future cell biology

Symmetry Breaking in C. elegans: Another Gift from the Sperm

Polarization of the C. elegans embryo depends on the sperm-contributed centrosome, which cues a retraction of the actomyosin cortex to the opposite end of the embryo by an unknown mechanism. New evidence reveals that the sperm donates a second polarizing cue that may locally relax the actomyosin cortex near the point of sperm entry

Embryonic polarity: A role for microtubules

Researchers have suspected that initial polarization of the Caenorhabditis elegans embryo might be directed by microtubules, but demonstrating this has faced obstacles. A new study has cleverly bypassed these obstacles

Tardigrade small heat shock proteins can limit desiccation-induced protein aggregation

Small heat shock proteins (sHSPs) are chaperones with well-characterized roles in heat stress, but potential roles for sHSPs in desiccation tolerance have not been as thoroughly explored. We identified nine sHSPs from the tardigrade Hypsibius exemplaris, each containing a conserved alpha-crystallin domain flanked by disordered regions. Many of these sHSPs are highly expressed. Multiple tardigrade and human sHSPs could improve desiccation tolerance of E. coli, suggesting that the capacity to contribute to desicco-protection is a conserved property of some sHSPs. Purification and subsequent analysis of two tardigrade sHSPs, HSP21 and HSP24.6, revealed that these proteins can oligomerize in vitro. These proteins limited heat-induced aggregation of the model enzyme citrate synthase. Heterologous expression of HSP24.6 improved bacterial heat shock survival, and the protein significantly reduced heat-induced aggregation of soluble bacterial protein. Thus, HSP24.6 likely chaperones against protein aggregation to promote heat tolerance. Furthermore, HSP21 and HSP24.6 limited desiccation-induced aggregation and loss of function of citrate synthase. This suggests a mechanism by which tardigrade sHSPs promote desiccation tolerance, by limiting desiccation-induced protein aggregation, thereby maintaining proteostasis and supporting survival. These results suggest that sHSPs provide a mechanism of general stress resistance that can also be deployed to support survival during anhydrobiosis.Small heat shock proteins from the tardigrade Hypsibius exemplaris are shown to provide a mechanism of stress resistance that can support not just heat tolerance but desiccation tolerance as well

The forces that position a mitotic spindle asymmetrically are tethered until after the time of spindle assembly

Regulation of the mitotic spindle's position is important for cells to divide asymmetrically. Here, we use Caenorhabditis elegans embryos to provide the first analysis of the temporal regulation of forces that asymmetrically position a mitotic spindle. We find that asymmetric pulling forces, regulated by cortical PAR proteins, begin to act as early as prophase and prometaphase, even before the spindle forms and shifts to a posterior position. The spindle does not shift asymmetrically during these early phases due to a tethering force, mediated by astral microtubules that reach the anterior cell cortex. We show that this tether is normally released after spindle assembly and independently of anaphase entry. Monitoring microtubule dynamics by photobleaching segments of microtubules during anaphase revealed that spindle microtubules do not undergo significant poleward flux in C. elegans. Together with the known absence of anaphase A, these data suggest that the major forces contributing to chromosome separation during anaphase originate outside the spindle. We propose that the forces positioning the mitotic spindle asymmetrically are tethered until after the time of spindle assembly and that these same forces are used later to drive chromosome segregation at anaphase

A Hypothesis for the Composition of the Tardigrade Brain and its Implications for Panarthropod Brain Evolution

Incredibly disparate brain types are found in Metazoa, which raises the question of how this disparity evolved. Ecdysozoa includes representatives that exhibit ring-like brains-the Cycloneuralia-and representatives that exhibit ganglionic brains-the Panarthropoda (Euarthropoda, Onychophora, and Tardigrada). The evolutionary steps leading to these distinct brain types are unclear. Phylogenomic analyses suggest that the enigmatic Tardigrada is a closely related outgroup of a Euarthropoda + Onychophora clade; as such, the brains of tardigrades may provide insight into the evolution of ecdysozoan brains. Recently, evolutionarily salient questions have arisen regarding the composition of the tardigrade brain. To address these questions, we investigated brain anatomy in four tardigrade species-Hypsibius dujardini, Milnesium n. sp., Echiniscus n. sp., and Batillipes n. sp.-that together span Tardigrada. Our results suggest that general brain morphology is conserved across Tardigrada. Based on our results we present a hypothesis that proposes direct parallels between the tardigrade brain and the segmental trunk ganglia of the tardigrade ventral nervous system. In this hypothesis, brain neuropil nearly circumscribes the tardigrade foregut. We suggest that the tardigrade brain retains aspects of an ancestral cycloneuralian brain, while exhibiting ganglionic structure characteristic of euarthropods and onychophorans

Mighty Knowledge

We often claim to know what might be—or probably is—the case. Modal knowledge along these lines creates a puzzle for information-sensitive semantics for epistemic modals. This paper develops a solution. We start with the idea that knowledge requires safe belief: a belief amounts to knowledge only if it could not easily have been held falsely. We then develop an interpretation of the modal operator in safety that allows it to non-trivially embed information-sensitive contents. The resulting theory avoids various paradoxes that arise from other accounts of modal knowledge. It also delivers plausible predictions about modal Gettier cases

How signaling between cells can orient a mitotic spindle

In multicellular animals, cell communication sometimes serves to orient the direction in which cells divide. Control of division orientation has been proposed to be critical for partitioning developmental determinants and for maintaining epithelial architecture. Surprisingly, there are few cases where we understand the mechanisms by which external cues, transmitted by intercellular signaling, specify the division orientation of animal cells. One would predict that cytosolic molecules or complexes exist that are capable of interpreting extrinsic cues, translating the positions of these cues into forces on microtubules of the mitotic spindle. In recent years, a key intracellular complex has been identified that is required for pulling forces on mitotic spindles in Drosophila, C. elegans and vertebrate systems. One member of this complex, a protein with tetratricopeptide repeat (TPR) and GoLoco (Gα-binding) domains, has been found localized in positions that coincide with the positions of spindle-orienting extracellular cues. Do TPR-GoLoco proteins function as conserved, spatially-regulated mediators of spindle orientation by intercellular signaling? Here, we review the relevant evidence among cases from diverse animal systems where this protein complex has been found to localize to specific cell-cell contacts and to be involved in orienting mitotic spindles

The PAR Proteins: Fundamental Players in Animal Cell Polarization

The par genes were discovered in genetic screens for regulators of cytoplasmic partitioning in the early embryo of C. elegans, and encode six different proteins required for asymmetric cell division by the worm zygote. Some of the PAR proteins are localized asymmetrically and form physical complexes with one another. Strikingly, the PAR proteins have been found to regulate cell polarization in many different contexts in diverse animals, suggesting they form part of an ancient and fundamental mechanism for cell polarization. Although the picture of how the PAR proteins function remains incomplete, cell biology and biochemistry are beginning to explain how PAR proteins polarize cells