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The role of nicotinic acetylcholine receptors in human cortical development remains largely unexplored. Here authors investigate CHRNA7 and CHRFAM7A, uncovering their involvement in radial glial cell proliferation and neuronal differentiation, and identify YAP1 as a downstream effector of cholinergic signaling.

Single-cell analysis of patient brains and cortical organoids links disrupted developmental metabolic reprogramming to postnatal synaptic dysfunction in dup15q syndrome, revealing shared neuronal changes with idiopathic autism.

The transcriptional profiles of radial glia are compared between humans and mice during neurogenesis, implicating the growth factor PDGFD and its receptor, PDGFRβ, in human but not mouse neocortical development.

An enormous expansion in cortical surface area was crucial for the evolution of the primate gyrencephalic cortex. Kriegstein and colleagues evaluate models of progenitor cell division that might underlie cortical expansion during development and provide an insight into this evolutionary step.

Single-cell proteomics maps protein dynamics in the developing human brain.

RNA-sequencing analysis of the prenatal human brain at different stages of development shows that areal transcriptional signatures are dynamic and coexist with developmental and cell-type signatures.

By capturing and manipulating the self-organizing capacity of pluripotent stem cells, researchers have established protocols for the production ofin vitrobrain-like 'organoids'. Di Lullo and Kriegstein evaluate approaches to organoid generation and consider their potential as models of brain development and disease.

Single-cell RNA sequencing clarifies the development and specification of neurons in the human cortex and shows that cell stress impairs this process in cortical organoids.

Tripotential intermediate progenitor cells are responsible for the local production of GABAergic neurons, oligodendrocyte precursor cells and astrocytes in the human neocortex.

A tri-omic atlas of the mouse brain from postnatal day 0 to P21 reveals that layer-specific projection neurons have a role in coordinating axonogenesis and myelination.

The progenitor cell populations that establish the developing human cortex exhibit distinct forms of apical–basal polarity. Kriegstein and colleagues review the mechanisms that regulate human cortical progenitor polarity, its importance for cortical development and the consequences of its disruption in neurological disorders.

A study presents a cross-species proteomic map of synapse development in neocortex and reveals that the human postsynaptic density assembly develops two to three times slower than that in macaques and mice.

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.

Analysis of cis-regulatory chromatin interactions, open chromatin and transcriptomes for different cell types isolated from mid-gestational human cortex samples provides insights into gene regulation during development.

Human neocortex expansion is partly due to neuronal production by outer radial glial cells. In the developing human cortex, LaMonica et al. find that horizontal divisions of ventricular radial glial cells produce outer radial glial cells displaying cell-intrinsic regulation of mitosis and spindle orientation.

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 authors report that radial glia–like (oRG) progenitor cells are present in the mouse embryonic cortex and that these cells arise from asymmetric divisions of radial glia. In turn, they undergo asymmetric divisions to generate neurons.

This paper describes the first evidence of a role for gap junctions in neuronal migration, and also shows that the adhesive properties of the gap junctions, not the conductivity of their channels, are important for the migration.

Chen et al. show that subtypes of immune cells in prenatal human brain promote angiogenesis in the germinal matrix. Conversely, in preterm infants, proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage.

In a feat of biological wizardry, one type of differentiated cell has been directly converted into another, completely distinct type. Notably, the approach does not require a stem-cell intermediate stage.

A stream of young neurons migrating into the entorhinal cortex (EC) continues postnatally in humans, but not in macaques; these young neurons, which belong to a unique class of local circuit cells, continue to be recruited in the EC during infancy and early childhood.

Immature excitatory neurons in the human amygdala persist throughout life and could be a substrate for plasticity. Here the authors find evidence that the maturation of these cells may be accelerated during puberty.

Eze et al. use single-cell sequencing and immunohistochemical validation to create an atlas of early human brain development. In the telencephalon, they discover a diversity of progenitor subtypes, including two that are enriched in humans.

Recent studies integrating multi-omics data with cell atlases across development for brains of humans and model organisms are revealing conserved and divergent patterns of brain development at the molecular and cellular levels, and linking these to complex behavioural and neuropsychiatric phenotypes.

In the nucleus, specific stretches of DNA are ‘anchored’ to distinct membrane-less compartments that harbor gene regulatory function. Using GO-CaRT, the authors discovered unique aspects of genome architecture in neural precursors in vivo, providing new insights into brain development and disease.

In the absence of progranulin, microglia enter a disease-specific state that causes endolysosomal dysfunction and neurodegeneration, and these microglia promote TDP-43 granule formation, nuclear pore defects and cell death specifically in excitatory neurons via the complement activation pathway.

The nomenclature for human multicellular models of nervous system development and disease, including organoids, assembloids and transplants, is discussed and a consensus framework is presented.

The dynamics of progenitor cells in human neocortex development has not been studied directly. Here, the authors timelapse image human neuroepithelial (NE) and radial glial (RG) cells in embryonic brain slices and find properties of NE cells and RG that are mimicked in cerebral organoids.

GABAergic cortical interneurons have important roles in the computations of neural circuits, but their developmental origin in primates is controversial. Here the authors characterize neural stem cell and progenitor cell organization in the developing human ganglionic eminences and reveal that, just as in rodents, they give rise to a majority of cortical GABAergic neurons.

The nuclei of radial glia divide and complete mitosis at the apical surface of the embryonic brain. They then migrate to the basal surface and back before dividing again. This study shows that these nuclei travel along microtubules, driven by KIF1A in the basal direction and by dynein in the apical direction.

The Human Cell Atlas (HCA) aims to characterize cells from diverse individuals across the globe to better understand human biology. Here, the authors lay out principles and action items that have been adopted to affirm HCA’s commitment to equity so that the atlas is beneficial to all of humanity.

In the adult brain, new neurons are generated from neural stem cells residing in the subventricular zone. Newborn neuroblasts release the transmitter GABA, which reduces the proliferation of stem cells—and thereby neurogenesis—by a nonsynaptic mechanism.

Numb is an important developmental protein that functions in fate determination, differentiation and cell maturation, but its role in mammalian neural progenitors has been controversial. A new paper uses a clever approach to attempt to reconcile the opposing views.

An international group of neuroscience researchers presents a framework for experimental designs for research using neural organoids and assembloids to study human development, evolution and disease.

Highly dynamic miRNA networks mediate developmental transitions during human brain development. Single-cell networks were detected by combining single-cell miRNA and mRNA profiling with HITS-CLIP analyzed with bipartite and co-expression networks.

Generation of human induced pluripotent stem cells from patient fibroblasts containing ring chromosomes with large deletions reveals that reprogrammed cells lose the abnormal chromosome and duplicate the wild-type homologue through compensatory uniparental disomy, suggesting that cellular reprogramming may hold potential for ‘chromosome therapy’.

Recruitment of young neurons to the hippocampus decreases rapidly during the first years of life, and neurogenesis does not continue, or is extremely rare, in the adult human brain.

This study presents a framework to evaluate rare and de novo variation from whole-genome sequencing (WGS). The work suggests that robust results from WGS studies will require large cohorts and strategies that consider the substantial multiple-testing burden.

Pollen et al. show that low-coverage RNA sequencing of single cells is a powerful approach for characterizing heterogeneous cell populations.

This Perspective outlines the Human Developmental Cell Atlas initiative, which uses state-of-the-art technologies to map and model human development across gestation, and discusses the early milestones that have been achieved.