Annual review of cell and developmental biology最新文献

Pediatric allergic disease is a significant health concern worldwide, and the prevalence of childhood eczema, asthma, allergic rhinitis, and food allergy continues to increase. Evidence to support specific interventions for the prevention of eczema, asthma, and allergic rhinitis is limited, and no consensus on prevention strategies has been reached. Randomized controlled trials investigating the prevention of food allergy via oral tolerance induction and the early introduction of allergenic foods have been successful in reducing peanut and egg allergy prevalence. Infant weaning guidelines in the United Sates were recently amended to actively encourage the introduction of peanut for prevention of peanut allergy.

Plants constantly perceive internal and external cues, many of which they need to address to safeguard their proper development and survival. They respond to these cues by selective activation of specific metabolic pathways involving a plethora of molecular players that act and interact in complex networks. In this review, we illustrate and discuss the complexity in the combinatorial control of plant specialized metabolism. We hereby go beyond the intuitive concept of combinatorial control as exerted by modular-acting complexes of transcription factors that govern expression of specialized metabolism genes. To extend this discussion, we also consider all known hierarchical levels of regulation of plant specialized metabolism and their interfaces by referring to reported regulatory concepts from the plant field. Finally, we speculate on possible yet-to-be-discovered regulatory principles of plant specialized metabolism that are inspired by knowledge from other kingdoms of life and areas of biological research.

Gene transcription by RNA polymerase II (Pol II) is the first step in the expression of the eukaryotic genome and a focal point for cellular regulation during development, differentiation, and responses to the environment. Two decades after the determination of the structure of Pol II, the mechanisms of transcription have been elucidated with studies of Pol II complexes with nucleic acids and associated proteins. Here we provide an overview of the nearly 200 available Pol II complex structures and summarize how these structures have elucidated promoter-dependent transcription initiation, promoter-proximal pausing and release of Pol II into active elongation, and the mechanisms that Pol II uses to navigate obstacles such as nucleosomes and DNA lesions. We predict that future studies will focus on how Pol II transcription is interconnected with chromatin transitions, RNA processing, and DNA repair.

Diverse factors including metabolism, chromatin remodeling, and mitotic kinetics influence development at the cellular level. These factors are well known to interact with the circadian transcriptional-translational feedback loop (TTFL) after its emergence. What is only recently becoming clear, however, is how metabolism, mitosis, and epigenetics may become organized in a coordinated cyclical precursor signaling module in pluripotent cells prior to the onset of TTFL cycling. We propose that both the precursor module and the TTFL module constrain cellular identity when they are active during development, and that the emergence of these modules themselves is a key lineage marker. Here we review the component pathways underlying these ideas; how proliferation, specification, and differentiation decisions in both developmental and adult stem cell populations are or are not regulated by the classical TTFL; and emerging evidence that we propose implies a primordial clock that precedes the classical TTFL and influences early developmental decisions.

Reconstitution is an experimental strategy that seeks to recapitulate biological events outside their natural contexts using a reduced set of components. Classically, biochemical reconstitution has been extensively applied to identify the minimal set of molecules sufficient for recreating the basic chemistry of life. By analogy, reconstitution approaches to developmental biology recapitulate aspects of developmental events outside an embryo, with the goal of revealing the basic genetic circuits or physical cues sufficient for recreating developmental decisions. The rapidly growing repertoire of genetic, molecular, microscopic, and bioengineering tools is expanding the complexity and precision of reconstitution experiments. We review the emerging field of synthetic developmental biology, with a focus on the ways in which reconstitution strategies and new biological tools have enhanced our modern understanding of fundamental questions in developmental biology.

The generation of all blood cell lineages (hematopoiesis) is sustained throughout the entire life span of adult mammals. Studies using cell transplantation identified the self-renewing, multipotent hematopoietic stem cells (HSCs) as the source of hematopoiesis in adoptive hosts and delineated a hierarchy of HSC-derived progenitors that ultimately yield mature blood cells. However, much less is known about adult hematopoiesis as it occurs in native hosts, i.e., without transplantation. Here we review recent advances in our understanding of native hematopoiesis, focusing in particular on the application of genetic lineage tracing in mice. The emerging evidence has established HSCs as the major source of native hematopoiesis, helped to define the kinetics of HSC differentiation, and begun exploring native hematopoiesis in stress conditions such as aging and inflammation. Major outstanding questions about native hematopoiesis still remain, such as its clonal composition, the nature of lineage commitment, and the dynamics of the process in humans.

The brain is our most complex organ. During development, neurons extend axons, which may grow over long distances along well-defined pathways to connect to distant targets. Our current understanding of axon pathfinding is largely based on chemical signaling by attractive and repulsive guidance cues. These cues instruct motile growth cones, the leading tips of growing axons, where to turn and where to stop. However, it is not chemical signals that cause motion-motion is driven by forces. Yet our current understanding of the mechanical regulation of axon growth is very limited. In this review, I discuss the origin of the cellular forces controlling axon growth and pathfinding, and how mechanical signals encountered by growing axons may be integrated with chemical signals. This mechanochemical cross talk is an important but often overlooked aspect of cell motility that has major implications for many physiological and pathological processes involving neuronal growth.

As cells grow, the size and number of their internal organelles increase in order to keep up with increased metabolic requirements. Abnormal size of organelles is a hallmark of cancer and an important aspect of diagnosis in cytopathology. Most organelles vary in either size or number, or both, as a function of cell size, but the mechanisms that create this variation remain unclear. In some cases, organelle size appears to scale with cell size through processes of relative growth, but in others the size may be set by either active measurement systems or genetic programs that instruct organelle biosynthetic activities to create organelles of a size appropriate to a given cell type.

Development encapsulates the morphogenesis of an organism from a single fertilized cell to a functional adult. A critical part of development is the specification of organ forms. Beyond the molecular control of morphogenesis, shape in essence entails structural constraints and thus mechanics. Revisiting recent results in biophysics and development, and comparing animal and plant model systems, we derive key overarching principles behind the formation of organs across kingdoms. In particular, we highlight how growing organs are active rather than passive systems and how such behavior plays a role in shaping the organ. We discuss the importance of considering different scales in understanding how organs form. Such an integrative view of organ development generates new questions while calling for more cross-fertilization between scientific fields and model system communities.