Volume 535 Number 7612

Editorials

Reward the forgotten foot soldiers of science p.323

The story of CRISPR–Cas9 gene editing has tended to focus on a few key players. But, as with any area of basic research, it takes a small army of talented researchers to make a discovery.

doi: 10.1038/535323a

News

News Features

The unsung heroes of CRISPR p.342

The soaring popularity of gene editing has made celebrities of the principal investigators who pioneered the field — but their graduate students and postdocs are often overlooked.

doi: 10.1038/535342a

News & Views

Cooling in the Antarctic p.358

The Antarctic Peninsula has been warming for many decades, but an analysis now reveals that it has cooled since the late 1990s. Inspection of the factors involved suggests that this is consistent with natural variability. See Letter p.411

doi: 10.1038/535358a

A surprise beginning for RNA p.359

Organic molecules called coenzymes are central to metabolism, but have also been found to act as components of RNA in bacteria. A study reveals how coenzymes are incorporated into RNA. See Letter p.444

doi: 10.1038/nature18908

Fishing for lessons on coral reefs p.361

A global study has identified coral reefs with greater fish biomass than would be predicted given human and environmental pressures. These outliers might teach us something about sustainable coral-reef management. See Letter p.416

doi: 10.1038/535361a

Attractive electrons from nanoengineering p.362

Electrons repel each other because they are negatively charged. An experiment now confirms a fifty-year-old theory that electrons can also attract one another as a result of repulsion from other electrons. See Letter p.395

doi: 10.1038/535362a

Nocturnal escape route for marsh gas p.363

A field study of methane emissions from wetlands reveals that more of the gas escapes through diffusive processes than was thought, mostly at night. Because methane is a greenhouse gas, the findings have implications for global warming.

doi: 10.1038/535363a

Pancreatic β-cell heterogeneity revisited p.365

Two analyses of insulin-producing β-cells reveal differences in what has long been considered a homogeneous population. These differences might reflect changes during maturation or ageing, or distinct cell lineages. See Letter p.430

doi: 10.1038/nature18907

Articles

A comprehensive transcriptional map of primate brain development p.367

A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.

doi: 10.1038/nature18637

Letters

Origin and implications of non-radial Imbrium Sculpture on the Moon p.391

The widespread rimmed grooves, lineations and elongate craters extending from the Imbrium impact basin on the Moon, termed the Imbrium Sculpture, includes a non-radial component that is used to infer that the Imbrium impactor was the size of a proto-planet—about half the diameter of Vesta.

doi: 10.1038/nature18278

Electron attraction mediated by Coulomb repulsion p.395

Experimental demonstration of excitonic attraction between two electrons is achieved in quantum devices made from carbon nanotubes, where the interaction between two electrons is reversed from repulsive to attractive owing to their strong Coulomb interaction with another electronic system.

doi: 10.1038/nature18639

Engineering and mapping nanocavity emission via precision placement of DNA origami p.401

The incorporation of large numbers of chemically diverse functional components into microfabricated structures at precise locations is challenging; now the precision placement of DNA origami by directed self-assembly is shown to overcome this problem for the purpose of reliably and controllably coupling molecular emitters to photonic crystal cavities.

doi: 10.1038/nature18287

Bright spots among the world’s coral reefs p.416

Data from over 2,500 reefs worldwide is used to identify 15 bright spots—sites where reef biomass is significantly higher than expected—and surveys of local experts in these areas suggest that strong sociocultural institutions and high levels of local engagement are among the factors supporting higher fish biomass.

doi: 10.1038/nature18607

Prefrontal neuronal assemblies temporally control fear behaviour p.420

Precise spike timing through the coordination and synchronization of neuronal assemblies is an efficient and flexible coding mechanism for sensory and cognitive processing. In cortical and subcortical areas, the formation of cell assemblies critically depends on neuronal oscillations, which can precisely control the timing of spiking activity. Whereas this form of coding has been described for sensory processing and spatial learning, its role in encoding emotional behaviour remains unknown. Fear behaviour relies on the activation of distributed structures, among which the dorsal medial prefrontal cortex (dmPFC) is known to be critical for fear memory expression. In the dmPFC, the phasic activation of neurons to threat-predicting cues, a spike-rate coding mechanism, correlates with conditioned fear responses and supports the discrimination between aversive and neutral stimuli. However, this mechanism does not account for freezing observed outside stimuli presentations, and the contribution of a general spike-time coding mechanism for freezing in the dmPFC remains to be established. Here we use a combination of single-unit and local field potential recordings along with optogenetic manipulations to show that, in the dmPFC, expression of conditioned fear is causally related to the organization of neurons into functional assemblies. During fear behaviour, the development of 4 Hz oscillations coincides with the activation of assemblies nested in the ascending phase of the oscillation. The selective optogenetic inhibition of dmPFC neurons during the ascending or descending phases of this oscillation blocks and promotes conditioned fear responses, respectively. These results identify a novel phase-specific coding mechanism, which dynamically regulates the development of dmPFC assemblies to control the precise timing of fear responses.

doi: 10.1038/nature18630

Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour p.425

Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, recent findings implicate meningeal immunity influencing behaviour, such as spatial learning and memory. Here we show that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto-cortical brain regions. Associations between rodent transcriptomes from brain and cellular transcriptomes in response to T-cell-derived cytokines suggest a strong interaction between social behaviour and interferon-γ (IFN-γ)-driven responses. Concordantly, we demonstrate that inhibitory neurons respond to IFN-γ and increase GABAergic (γ-aminobutyric-acid) currents in projection neurons, suggesting that IFN-γ is a molecular link between meningeal immunity and neural circuits recruited for social behaviour. Meta-analysis of the transcriptomes of a range of organisms reveals that rodents, fish, and flies elevate IFN-γ/JAK-STAT-dependent gene signatures in a social context, suggesting that the IFN-γ signalling pathway could mediate a co-evolutionary link between social/aggregation behaviour and an efficient anti-pathogen response. This study implicates adaptive immune dysfunction, in particular IFN-γ, in disorders characterized by social dysfunction and suggests a co-evolutionary link between social behaviour and an anti-pathogen immune response driven by IFN-γ signalling.

doi: 10.1038/nature18626

Identification of proliferative and mature β-cells in the islets of Langerhans p.430

Insulin-dependent diabetes is a complex multifactorial disorder characterized by loss or dysfunction of β-cells. Pancreatic β-cells differ in size, glucose responsiveness, insulin secretion and precursor cell potential; understanding the mechanisms that underlie this functional heterogeneity might make it possible to develop new regenerative approaches. Here we show that Fltp (also known as Flattop and Cfap126), a Wnt/planar cell polarity (PCP) effector and reporter gene, acts as a marker gene that subdivides endocrine cells into two subpopulations and distinguishes proliferation-competent from mature β-cells with distinct molecular, physiological and ultrastructural features. Genetic lineage tracing revealed that endocrine subpopulations from Fltp-negative and -positive lineages react differently to physiological and pathological changes. The expression of Fltp increases when endocrine cells cluster together to form polarized and mature 3D islet mini-organs. We show that 3D architecture and Wnt/PCP ligands are sufficient to trigger β-cell maturation. By contrast, the Wnt/PCP effector Fltp is not necessary for β-cell development, proliferation or maturation. We conclude that 3D architecture and Wnt/PCP signalling underlie functional β-cell heterogeneity and induce β-cell maturation. The identification of Fltp as a marker for endocrine subpopulations sheds light on the molecular underpinnings of islet cell heterogeneity and plasticity and might enable targeting of endocrine subpopulations for the regeneration of functional β-cell mass in diabetic patients.

doi: 10.1038/nature18624

The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA p.444

The chemical nature of the 5′ end of RNA is a key determinant of RNA stability, processing, localization and translation efficiency, and has been proposed to provide a layer of ‘epitranscriptomic’ gene regulation. Recently it has been shown that some bacterial RNA species carry a 5′-end structure reminiscent of the 5′ 7-methylguanylate ‘cap’ in eukaryotic RNA. In particular, RNA species containing a 5′-end nicotinamide adenine dinucleotide (NAD+) or 3′-desphospho-coenzyme A (dpCoA) have been identified in both Gram-negative and Gram-positive bacteria. It has been proposed that NAD+, reduced NAD+ (NADH) and dpCoA caps are added to RNA after transcription initiation, in a manner analogous to the addition of 7-methylguanylate caps. Here we show instead that NAD+, NADH and dpCoA are incorporated into RNA during transcription initiation, by serving as non-canonical initiating nucleotides (NCINs) for de novo transcription initiation by cellular RNA polymerase (RNAP). We further show that both bacterial RNAP and eukaryotic RNAP II incorporate NCIN caps, that promoter DNA sequences at and upstream of the transcription start site determine the efficiency of NCIN capping, that NCIN capping occurs in vivo, and that NCIN capping has functional consequences. We report crystal structures of transcription initiation complexes containing NCIN-capped RNA products. Our results define the mechanism and structural basis of NCIN capping, and suggest that NCIN-mediated ‘ab initio capping’ may occur in all organisms.

doi: 10.1038/nature18622