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The Turing, or reaction-diffusion (RD), model is one of the best-known theoretical models used to explain self-regulated pattern formation in the developing animal embryo. Although its real-world relevance was long debated, a number of compelling examples have gradually alleviated much of the skepticism surrounding the model. The RD model can generate a wide variety of spatial patterns, and mathematical studies have revealed the kinds of interactions required for each, giving this model the potential for application as an experimental working hypothesis in a wide variety of morphological phenomena. In this review, we describe the essence of this theory for experimental biologists unfamiliar with the model, using examples from experimental studies in which the RD model is effectively incorporated.

Myosin-II in epithelial morphogenesis Myosin-II has a central role in generating the forces that drive cell shape changes during embryo development. Thomas Lecuit and colleagues study germ-band extension in Drosophila , in which epithelial cells undergo an ordered process of intercalation resulting in tissue extension through remodelling of cell junctions. They find that cell-junction shrinkage is driven by polarized flow of medial myosin-II pulses towards junctions, which organizes the whole process of intercalation. In addition, the flow of myosin-II is driven by the polarized distribution of E-cadherin/β-catenin/ α-catenin complexes at adherens junctions. Thus, epithelial morphogenesis is driven by polarized contractile actomyosin flows emerging from interactions between E-cadherin and actomyosin networks. Here, germ-band extension in Drosophila is studied in which epithelial cells undergo an ordered process of intercalation resulting in tissue extension through remodelling of cell junctions. Cell junction shrinkage is driven by polarized flow of medial Myosin-II pulses towards junctions which organizes the whole process of intercalation. The flow of Myosin II is driven by the polarized distribution of E-cadherin complexes at adherens junctions. Thus, epithelial morphogenesis is driven by polarized contractile actomyosin flows emerging from interactions between E-cadherin and actomyosin networks. Force generation by Myosin-II motors on actin filaments drives cell and tissue morphogenesis 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 . In epithelia, contractile forces are resisted at apical junctions by adhesive forces dependent on E-cadherin 16 , which also transmits tension 6 , 17 , 18 , 19 . During Drosophila embryonic germband extension, tissue elongation is driven by cell intercalation 20 , which requires an irreversible and planar polarized remodelling of epithelial cell junctions 4 , 5 . We investigate how cell deformations emerge from the interplay between force generation and cortical force transmission during this remodelling in Drosophila melanogaster . The shrinkage of dorsal–ventral-oriented (‘vertical’) junctions during this process is known to require planar polarized junctional contractility by Myosin II (refs 4 , 5 , 7 , 12 ). Here we show that this shrinkage is not produced by junctional Myosin II itself, but by the polarized flow of medial actomyosin pulses towards ‘vertical’ junctions. This anisotropic flow is oriented by the planar polarized distribution of E-cadherin complexes, in that medial Myosin II flows towards ‘vertical’ junctions, which have relatively less E-cadherin than transverse junctions. Our evidence suggests that the medial flow pattern reflects equilibrium properties of force transmission and coupling to E-cadherin by α-Catenin. Thus, epithelial morphogenesis is not properly reflected by Myosin II steady state distribution but by polarized contractile actomyosin flows that emerge from interactions between E-cadherin and actomyosin networks.

Key Points A neuron can rapidly combine and transform the information it receives through its synaptic inputs before the information is converted into neuronal output. This transformation can be defined by the neuronal input–output (I–O) relationship. Changes in the I–O relationship can correspond to distinct arithmetic operations. During sustained rate-coded signalling, the neuron operates as a signal integrator (over a given time-window) and the neuronal I–O relationship is defined as the dependence of sustained output firing rate on the input rate. During sparse temporally correlated signalling, the neuron acts as a coincidence detector and the I–O relationship can be defined in terms of the dependence of spike probability on the number of coincident inputs or their temporal correlation. Additive and subtractive operations performed on driving inputs by distinct modulatory synaptic input correspond to shifts in the I–O relationship, without a change of shape. Multiplicative and divisive operations correspond to increases or decreases in the slope, or gain, of the I–O relationship. Both of these operations have been observed in vivo during different tasks. Additive operations are essential for linearly combining signals and for controlling the number of inputs required for signalling. In the temporal domain, additive operations control the width of the temporal correlation window that the neuron can respond to and thus the temporal properties of signals that can propagate through the network. Multiplicative operations, or gain changes, are important for signal amplification, normalization and preventing saturation of firing, thereby allowing efficient information transmission. Gain changes are essential for coordinate transforms and have been proposed to control the functional connectivity of networks. In the temporal domain, neural gain also controls the 'roll-off' of the temporal correlation window for synaptic integration. Both morphologically simple neurons and those with extensive dendritic trees possess a number of biophysical mechanisms, including inhibition, short-term synaptic plasticity, synaptic noise and somatic and dendritic conductances that enable them to perform additive and multiplicative operations on their synaptic inputs. Some biophysical mechanisms, such as voltage noise, are general in that they perform the same arithmetic operation (multiplication) on sustained rate-coded and sparse temporally coded signals. However, others seem to be tuned for either sustained rate-coding or sparse coding regimes. Widespread presynaptic and dendritic mechanisms enable spatially segregated inputs to be multiplied together, although other local dendritic conductances seem to be tuned to detect spatio-temporally correlated input onto a specific dendritic branch. An extensive tool kit of nonlinear mechanisms confers considerable computational power on individual neurons, enabling them to perform a range of arithmetic operations on signals encoded in a variety of different ways. Individual neurons transform the relationship between synaptic input and output firing by utilizing both linear and nonlinear mechanisms. Angus Silver discusses the various underlying biophysical mechanisms in relation to the complexity of neuronal morphology and the neural coding regimes in which they are likely to operate. The vast computational power of the brain has traditionally been viewed as arising from the complex connectivity of neural networks, in which an individual neuron acts as a simple linear summation and thresholding device. However, recent studies show that individual neurons utilize a wealth of nonlinear mechanisms to transform synaptic input into output firing. These mechanisms can arise from synaptic plasticity, synaptic noise, and somatic and dendritic conductances. This tool kit of nonlinear mechanisms confers considerable computational power on both morphologically simple and more complex neurons, enabling them to perform a range of arithmetic operations on signals encoded in a variety of different ways.

Key Points Resilient individuals demonstrate adaptive psychological and physiological stress responses to acute stress, trauma or more chronic forms of adversity. Resilience is an active process, not simply the absence of changes induced by stress. Examining stress responses at multiple phenotypic levels can help to delineate an integrative model of resilience. Positive emotions and cognitive reappraisal promote adaptive coping strategies and resilience. Complex interactions between an individual's genetic make-up and their history of exposure to environmental stressors influence the adaptability of stress response systems and neural circuitry function. Progress is being made in identifying the neural circuits in the brain that mediate resilience. Recent work has begun to identify specific changes in gene expression and chromatin remodelling (that is, epigenetic adaptations) that underlie resilience. Although stress is associated with many physical and mental illnesses, most individuals cope well with it. Feder and colleagues review the factors that underlie stress resilience, showing that it involves adaptive changes in specific neural circuits, neuromodulator levels and molecular pathways. Every individual experiences stressful life events. In some cases acute or chronic stress leads to depression and other psychiatric disorders, but most people are resilient to such effects. Recent research has begun to identify the environmental, genetic, epigenetic and neural mechanisms that underlie resilience, and has shown that resilience is mediated by adaptive changes in several neural circuits involving numerous neurotransmitter and molecular pathways. These changes shape the functioning of the neural circuits that regulate reward, fear, emotion reactivity and social behaviour, which together are thought to mediate successful coping with stress.

During animal development, several planar cell polarity (PCP) pathways control tissue shape by coordinating collective cell behavior. Here, we characterize by means of multiscale imaging epithelium morphogenesis in the Drosophila dorsal thorax and show how the Fat/Dachsous/Four-jointed PCP pathway controls morphogenesis. We found that the proto-cadherin Dachsous is polarized within a domain of its tissue-wide expression gradient. Furthermore, Dachsous polarizes the myosin Dachs, which in turn promotes anisotropy of junction tension. By combining physical modeling with quantitative image analyses, we determined that this tension anisotropy defines the pattern of local tissue contraction that contributes to shaping the epithelium mainly via oriented cell rearrangements. Our results establish how tissue planar polarization coordinates the local changes of cell mechanical properties to control tissue morphogenesis.

Key Points The axon initial segment (AIS) functions as both a structural and a functional bridge between neuronal input and output. The AIS is characterized by clustered voltage-gated Na + and K + channels that integrate synaptic inputs and initiate action potentials. The AIS also has high densities of cell adhesion molecules, signalling proteins and cytoskeletal proteins and scaffolds. The AIS regulates three kinds of neuronal polarity: functional polarity (that is, the directional propagation of information), anatomical polarity (that is, the distinction between axonal and somatodendritic domains) and subcellular polarity (that is, the restricted localization of ion channels, organelles and protein complexes to distinct membrane domains or cellular compartments). The assembly of the AIS protein complexes and establishment of AIS subcellular polarity depends on the cytoskeletal scaffolding protein ankyrin G (AnkG, also known as ANK3). Thus, AnkG is the master organizer of the AIS. The maintenance of neuronal polarity depends on a physical barrier that is located at the AIS and restricts lipids, membrane and cytoplasmic proteins and vesicular cargoes to somatodendritic or axonal domains. Actin, microtubules and the high density of proteins at the AIS all contribute to this barrier. AnkG is also required for the functioning of the barrier, including the regulation of actin and microtubules and protein retention at the AIS. Loss of AnkG results in dismantling of the AIS and the axon acquiring the structural and molecular properties of dendrites. The AIS cytoskeleton can be disrupted by diseases and injuries, causing loss of clustered ion channels and anatomical polarity. Loss of neuronal polarity may be a previously overlooked consequence of nervous system injury. The AIS can be viewed as the 'gatekeeper' of nervous system function, and the modulation of AIS properties can have dramatic consequences for neuronal excitability and circuit properties. Neuronal activity can modulate the location of the AIS, which in turn influences the input–output response of the neuron. In contrast to synaptic plasticity, AIS plasticity occurs over hours and even days, and therefore may result in changes to the neuronal input–output function that persist over long periods of time. Polarity is an essential requirement for neuronal function. Matthew Rasband describes the role of the axon initial segment in the development and maintenance of neuronal polarity and discusses how its disruption can lead to disorders of the nervous system. Ion channel clustering at the axon initial segment (AIS) and nodes of Ranvier has been suggested to be a key evolutionary innovation that enabled the development of the complex vertebrate nervous system. This innovation epitomizes a signature feature of neurons, namely polarity. The mechanisms that establish neuronal polarity, channel clustering and axon–dendrite identity during development are becoming clearer. However, much less is known about how polarity is maintained throughout life. Here, I review the role of the AIS in the development and maintenance of neuronal polarity and discuss how disrupted polarity may be a common component of many diseases and injuries that affect the nervous system.

Little is known about how organ growth is monitored and coordinated with the developmental timing in complex organisms. In insects, impairment of larval tissue growth delays growth and morphogenesis, revealing a coupling mechanism. We carried out a genetic screen in Drosophila to identify molecules expressed by growing tissues participating in this coupling and identified dilp8 as a gene whose silencing rescues the developmental delay induced by abnormally growing tissues. dilp8 is highly induced in conditions where growth impairment produces a developmental delay. dilp8 encodes a peptide for which expression and secretion are sufficient to delay metamorphosis without affecting tissue integrity. We propose that Dilp8 peptide is a secreted signal that coordinates the growth status of tissues with developmental timing.

Listen to an interview with David Scadden on the stem cells podcast Stem-cell populations are established in ‘niches’ — specific anatomic locations that regulate how they participate in tissue generation, maintenance and repair. The niche saves stem cells from depletion, while protecting the host from over-exuberant stem-cell proliferation. It constitutes a basic unit of tissue physiology, integrating signals that mediate the balanced response of stem cells to the needs of organisms. Yet the niche may also induce pathologies by imposing aberrant function on stem cells or other targets. The interplay between stem cells and their niche creates the dynamic system necessary for sustaining tissues, and for the ultimate design of stem-cell therapeutics.

Developing animals frequently adjust their growth programs and/or their maturation or metamorphosis to compensate for growth disturbances (such as injury or tumor) and ensure normal adult size. Such plasticity entails tissue and organ communication to preserve their proportions and symmetry. Here, we show that imaginai discs autonomously activate DILP8, a Drosophilo insulin-like peptide, to communicate abnormal growth and postpone maturation. DILP8 delays metamorphosis by inhibiting ecdysone biosynthesis, slowing growth in the imaginai discs, and generating normal-sized animals. Loss of dilp8 yields asymmetric individuals with an unusually large variation in size and a more varied time of maturation. Thus, DILP8 is a fundamental element of the hitherto ill-defined machinery governing the plasticity that ensures developmental stability and robustness.

Quantifying cell behaviors in animal early embryogenesis remains a challenging issue requiring in toto imaging and automated image analysis. We designed a framework for imaging and reconstructing unstained whole zebrafish embryos for their first 10 cell division cycles and report measurements along the cell lineage with micrometer spatial resolution and minute temporal accuracy. Point-scanning multiphoton excitation optimized to preferentially probe the innermost regions of the embryo provided intrinsic signals highlighting all mitotic spindles and cell boundaries. Automated image analysis revealed the phenomenology of cell proliferation. Blastomeres continuously drift out of synchrony. After the 32-cell stage, the cell cycle lengthens according to cell radial position, leading to apparent division waves. Progressive amplification of this process is the rule, contrasting with classical descriptions of abrupt changes in the system dynamics.