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A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Populations of astrocytes in the spinal cord are shown to express region-specific genes, with ventral astrocyte-encoded Sema3a necessary for proper motor neuron circuit organization and typical sensory afferent projection patterns; these findings suggest that astrocytes provide a positional cue for maintaining proper circuit formation and refinement.

Neonatal gyrated brains harbor an elaborate subventricular zone, termed the Arc, supporting cortical migratory streams of diverse interneurons.

Despite their structural similarities and seemingly coordinated expression patterns, oligodendrocyte transcription factor 1 (OLIG1) and OLIG2 have largely non-overlapping roles in CNS development, brain diseases and neural repair. Here, the authors review the molecular factors that may account for the divergent functions of these proteins.

Here the authors show that ventrally derived oligodendrocytes (OLs) can myelinate areas usually populated by dorsally derived OLs but cannot functionally compensate, as animals populated only by ventrally derived OLs show locomotor and cognitive deficits.

Emerging evidence suggests that astrocytes may be as diverse in their physiological and functional characteristics as neurons. Ben Haim and Rowitch describe astrocyte heterogeneity, consider the mechanisms by which such diversity may arise and discuss the consequences of its disruption in disease.

Postnatal growth of the pons is not well characterized. Here the authors show that growth of the murine pons is fastest during postnatal day 0–4, a period preceding myelination, and is primarily driven by an expansion of the oligodendrocyte population that derive from Sox2⁺Olig2⁺progenitors.

Comprehensive factor analysis of core diagnostic features provides insights into the complex genetic architecture underlying phenotypic heterogeneity in autism.

These two studies show that primary cilia can either mediate or suppress tumorigenesis in models of basal cell carcinoma and medulloblastoma, respectively, depending on the nature of the initial oncogenic event (pages 994–996) and (pages 1055–1061).

A new spatial transcriptomic approach reveals astrocyte heterogeneity across layers of the mammalian cerebral cortex. Astrocytes diversify into superficial-, mid- and deep-layer subtypes distinct from neuronal laminae, yet instructed by neuronal cues.

Using the lifespan brain chart and two large-scale cross-cultural consortia (ABIDE and CABIC), we disentangle the heterogeneity of brain morphology in ASD into two structural impairment pathways that could disrupt sensory to association functions.

Single-cell RNA sequencing was used to construct a map of gene expression in lesions from brains of patients with multiple sclerosis, revealing distinct lineage- and region-specific transcriptomic changes associated with selective cortical neuron damage and glial activation.

A reactive astrocyte subtype termed A1 is induced after injury or disease of the central nervous system and subsequently promotes the death of neurons and oligodendrocytes.

Oligodendrocyte progenitor cell (OPC) proliferation is crucial for regeneration after hypoxic lesions in mice, a model of diffuse white matter injury of premature infants. Here, the authors show that the histone deacetylase Sirt1 is a Cdk2-dependent mediator of OPC proliferation and OPC response to hypoxia.

Premyelinating oligodendrocytes are vulnerable to hypoxic injuries, especially during the neonatal period. Here, Fancy et al. find that the Wnt scaffolding molecule Axin2 is crucial for normal remyelination after hypoxic injuries and demonstrate that pharmacological inhibition of tankyrase, which stabilizes Axin2 levels, can promote oligodendrocyte differentiation and recovery after hypoxic and demyelinating injuries.

Transcriptomes of about 70,000 single cells from first-trimester deciduas and placentas reveal subsets of perivascular, stromal and natural killer cells in the decidua, with distinct immunomodulatory profiles that regulate the environment necessary for successful placentation.

Much of what we know about the signal transduction machinery of the canonical Wnt pathway comes from studying the colon, where low- versus high-activity Wnt signaling states are known to distinguish normal colon epithelium turnover from colorectal cancer. Here, Fancy et al. demonstrate that a pathological Wnt activity state akin to that in colon cancer exists in oligodendrocyte precursor cells in human neonatal white matter injury, which leads to detrimental maturation arrest of these cells. These oligodendrocyte precursors in human newborn brain injury express multiple genes in common with colon cancer, demonstrating a pathological Wnt tone in non-genetic human disease.

In the mammalian brain, the subventricular zone (SVZ) produces neural progenitor cells that migrate into the cortex to populate the upper layers. In humans this region is massively expanded, producing an outer SVZ (OSVZ). Here, live-cell imaging of developing human tissue was used to show that the OSVZ has similar characteristics to the SVZ, with progenitor cells proliferating in a way that depends on the Notch protein. The findings have implications for our understanding of how the complex human brain evolved.

The methylation of DNA in 5′ promoter regions suppresses gene expression, but what is the role of DNA methylation in the bodies of genes? Here, a map of DNA methylation is generated from human brain tissue; it is found that most methylated CpG islands are within intragenic and intergenic regions, rather than within promoters. It is proposed that intragenic methylation regulates the expression of alternative gene transcripts in different tissues and cell types.

Aged progenitor cells in the rat central nervous system can be made to behave as young cells by reducing the stiffness of the tissue microenvironment, or by inhibiting the mechanosensitive protein PIEZO1.

Good–bad binary classifications fail to describe reactive astrocytes in CNS disorders. Here, 81 researchers reach consensus on widespread misconceptions and provide definitions and recommendations for future research on reactive astrocytes.

Brain cancer encompasses a diverse range of complex malignancies, many of which are associated with a poor prognosis and require more effective treatments. In this Position Paper, an international panel of clinicians and laboratory-based scientists convened by Cancer Research UK identify and discuss seven challenges that must be overcome if we are to cure all patients with a brain tumour.

Michael Taylor and colleagues identify copy number aberrations of genes with critical roles in writing, reading, removing and blocking the state of histone lysine methylation, indicating that defective control of the histone code contributes to the pathogenesis of medulloblastoma.

As the mortality rates of premature and newborn babies have decreased, the incidence of neurological morbidity in these neonates has increased. Bonifacio et al. highlight advances in the care of neonates who have sustained a neurological insult, discussing available treatments and therapies, and the utility of brain monitoring techniques to predict long-term neurological outcomes. They also present a new model of care for the treatment of neonates with brain injury.

The size and the extent of gyrification of the cerebral cortex both influence brain function in mammals. In this Review, Sun and Hevner examine the mechanisms underlying cortical growth and folding, and discuss how dysfunction in these processes leads to cortical malformations.

The human left and right hemispheres have distinct functions. Sun and Walsh discuss recent genetic, imaging and neurological studies in an attempt to unravel the molecular mechanisms of brain asymmetry and handedness and to understand their evolutionary underpinning.