Seminars in cell & developmental biology最新文献

The process by which biological systems such as cells, tissues and organisms acquire shape has been named as morphogenesis and it is central to a plethora of biological contexts including embryo development, wound healing, or even cancer. Morphogenesis relies in both self-organising properties of the system and in environmental inputs (biochemical and biophysical). The classical view of morphogenesis is based on the study of external biochemical molecules, such as morphogens. However, recent studies are establishing that the mechanical environment is also used by cells to communicate within tissues, suggesting that this mechanical crosstalk is essential to synchronise morphogenetic transitions and self-organisation. In this article we discuss how tissue interaction drive robust morphogenesis, starting from a classical biochemical view, to finalise with more recent advances on how the biophysical properties of a tissue feedback with their surroundings to allow form acquisition. We also comment on how in silico models aid to integrate and predict changes in cell and tissue behaviour. Finally, considering recent advances from the developmental biomechanics field showing that mechanical inputs work as cues that promote morphogenesis, we invite to revisit the concept of morphogen.

Scientific knowledge in the field of cell biology and mechanobiology heavily leans on cell-based in vitro experiments and models that favor the examination and comprehension of certain biological processes and occurrences across a variety of environments. Cell culture assays are an invaluable instrument for a vast spectrum of biomedical and biophysical investigations. The quality of experimental models in terms of simplicity, reproducibility, and combinability with other methods, and in particular the scale at which they depict cell fate in native tissues, is critical to advancing the knowledge of the comprehension of cell-cell and cell-matrix interactions in tissues and organs. Typically, in vitro models are centered on the experimental tinkering of mammalian cells, most often cultured as monolayers on planar, two-dimensional (2D) materials. Notwithstanding the significant advances and numerous findings that have been accomplished with flat biology models, their usefulness for generating further new biological understanding is constrained because the simple 2D setting does not reproduce the physiological response of cells in natural living tissues. In addition, the co-culture systems in a 2D stetting weakly mirror their natural environment of tissues and organs. Significant advances in 3D cell biology and matrix engineering have resulted in the creation and establishment of a new type of cell culture shapes that more accurately represents the in vivo microenvironment and allows cells and their interactions to be analyzed in a biomimetic approach. Contemporary biomedical and biophysical science has novel advances in technology that permit the design of more challenging and resilient in vitro models for tissue engineering, with a particular focus on scaffold- or hydrogel-based formats, organotypic cultures, and organs-on-chips, which cover the purposes of co-cultures. Even these complex systems must be kept as simplified as possible in order to grasp a particular section of physiology too very precisely. In particular, it is highly appreciated that they bridge the space between conventional animal research and human (patho)physiology. In this review, the recent progress in 3D biomimetic culturation is presented with a special focus on co-cultures, with an emphasis on the technological building blocks and endothelium-based co-culture models in cancer research that are available for the development of more physiologically relevant in vitro models of human tissues under normal and diseased conditions. Through applications and samples of various physiological and disease models, it is possible to identify the frontiers and future engagement issues that will have to be tackled to integrate synthetic biomimetic culture systems far more successfully into biomedical and biophysical investigations.

Animal tissues are composed of heterogenous cells, and their sorting into different compartments of the tissue is a pivotal process for organogenesis. Cells accomplish sorting by themselves—it is well known that singly dispersed cells can self-organize into tissue-like structures in vitro. Cell sorting is regulated by both biochemical and physical mechanisms. Adhesive proteins connect cells together, selecting particular partners through their specific binding properties, while physical forces, such as cell-cortical tension, control the cohesiveness between cells and in turn cell assembly patterns in mechanical ways. These processes cooperate in determining the overall cell sorting behavior. This article focuses on the ‘cadherin’ family of adhesion molecules as a biochemical component of cell-cell interactions, addressing how they regulate cell sorting by themselves or by cooperating with other factors. New ideas beyond the classical models of cell sorting are also discussed.

Due to the current relevance of pulmonary toxicology (with focus upon air pollution and the inhalation of hazardous materials), it is important to further develop and implement physiologically relevant models of the entire respiratory tract. Lung model development has the aim to create human relevant systems that may replace animal use whilst balancing cost, laborious nature and regulatory ambition. There is an imperative need to move away from rodent models and implement models that mimic the holistic characteristics important in lung function. The purpose of this review is therefore, to describe and identify the various alternative models that are being applied towards assessing the pulmonary toxicology of inhaled substances, as well as the current and potential developments of various advanced models and how they may be applied towards toxicology testing strategies. These models aim to mimic various regions of the lung, as well as implementing different exposure methods with the addition of various physiologically relevent conditions (such as fluid-flow and dynamic movement). There is further progress in the type of models used with focus on the development of lung-on-a-chip technologies and bioprinting, as well as and the optimization of such models to fill current knowledge gaps within toxicology.

In development, tissue shape changes and gene expression patterns give rise to morphogenesis. Understanding tissue shape changes requires the analysis of mechanical properties of the tissue such as tissue rigidity, cell influx from neighboring tissues, cell shape changes and cell proliferation. Local and global gene expression patterns can be influenced by neighbor exchange and tissue shape changes. Here we review recent studies on the mechanisms for tissue elongation and its influences on dynamic gene expression patterns by focusing on vertebrate somitogenesis. We first introduce mechanical and biochemical properties of the segmenting tissue that drive tissue elongation. Then, we discuss patterning in the presence of cell mixing, scaling of signaling gradients, and dynamic phase waves of rhythmic gene expression under tissue shape changes. We also highlight the importance of theoretical approaches to address the relation between tissue shape changes and patterning.

The ubiquitin proteasome system maintains protein homeostasis by regulating the breakdown of misfolded proteins, thereby preventing misfolded protein aggregates. The efficient elimination is vital for preventing damage to the cell by misfolded proteins, known as proteotoxic stress. Proteotoxic stress can lead to the collapse of protein homeostasis and can alter the function of the ubiquitin proteasome system. Conversely, impairment of the ubiquitin proteasome system can also cause proteotoxic stress and disrupt protein homeostasis. This review examines two impacts of proteotoxic stress, 1) disruptions to ubiquitin homeostasis (ubiquitin stress) and 2) disruptions to proteasome homeostasis (proteasome stress). Here, we provide a mechanistic description of the relationship between proteotoxic stress and the ubiquitin proteasome system. This relationship is illustrated by findings from several protein misfolding diseases, mainly neurodegenerative diseases, as well as from basic biology discoveries from yeast to mammals. In addition, we explore the importance of the ubiquitin proteasome system in endoplasmic reticulum quality control, and how proteotoxic stress at this organelle is alleviated. Finally, we highlight how cells utilize the ubiquitin proteasome system to adapt to proteotoxic stress and how the ubiquitin proteasome system can be genetically and pharmacologically manipulated to maintain protein homeostasis.

During lytic replication, herpesviruses express their genes in a temporal cascade culminating in expression of “late” genes. Two subfamilies of herpesviruses, the beta- and gammaherpesviruses (including human herpesviruses cytomegalovirus, Epstein-Barr virus, and Kaposi’s sarcoma-associated herpesvirus), use a unique strategy to facilitate transcription of late genes. They encode six essential viral transcriptional activators (vTAs) that form a complex at a subset of late gene promoters. One of these vTAs is a viral mimic of host TATA-binding protein (vTBP) that recognizes a strikingly minimal cis-acting element consisting of a modified TATA box with a TATTWAA consensus sequence. vTBP is also responsible for recruitment of cellular RNA polymerase II (Pol II). Despite extensive work in the beta/gammaherpesviruses, the function of the other five vTAs remains largely unknown. The vTA complex and Pol II assemble on the promoter into a viral preinitiation complex (vPIC) to facilitate late gene transcription. Here, we review the properties of the vTAs and the promoters on which they act.