This Review discusses how rare-disease-causing variants in the noncoding genome impact gene regulation, why these examples are so few and how new approaches could accelerate discovery of noncoding var...

Nature Cell Biology - This Perspective presents a set of attributes by which to evaluate human stem cell-based embryo models that not only include morally relevant embryo features but also take...

The mammalian genome is organised into large topologically associating domains (TADs) and smaller sub-TADs or enhancer-promoter loops, which may contribute to the regulation of gene expression. These ...

Facial development is highly sensitive to genetic and environmental perturbation, with craniofacial malformation associated with over one-third of congenital birth defects. The face arises during an early and largely inaccessible window of embryonic development, with a large contribution from transient and multipotent cranial neural crest cells (CNCCs). Assessment of the molecular and cellular mechanisms driving normal and disordered human facial development therefore relies greatly on the use of in vitro cellular models. Here, we adapted a neurosphere-based CNCC differentiation protocol to facilitate robust quantification of early specification and migration events. Introduction of single-cell aggregation with arrayed plating enabled standardisation of neurosphere size, growth and patterning. Inclusion of fibronectin coating enhanced the efficiency of neurosphere attachment and synchronicity of CNCC migration timing. To demonstrate application of the Array-CNCC method, we developed a strategy for mosaic co-culture, which can facilitate differentiation of wildtype untreated cells directly alongside cells exposed to distinct drug treatments or genetic alterations. Finally, we present a screening approach which we use to test the impact of distinct extracellular matrix components on neurosphere morphology, CNCC migration and gene expression. Together, the Array-CNCC method is highly amenable to quantitative phenotyping and screening approaches, enabling enhanced craniofacial disease modelling with both cellular and molecular readouts. ### Competing Interest Statement The authors have declared no competing interest. Medical Research Council, MC\_UU\_00035/12, MC\_ST\_00035 Wellcome Trust, https://ror.org/029chgv08, 227712/Z/23/Z

Author summary One powerful way to study regulation is to examine hybrids between two inbred species, where each gene has two distinct parental copies, or alleles. Measuring how much each allele is ex...

Neutrophils infiltrate glioblastomas with the capacity to engage pro/anti tumoural responses. Here the authors developed proteomic workflows to stratify neutrophil heterogeneity by function. This work...

Histone H3 lysine 4 trimethylation (H3K4me3) at gene promoters is thought to play a central role in gene transcription. H3K4 methylation is deposited by the SET1 (A/B) and MLL (1-4) multi-protein comp...

JASPAR is the largest open-access database of curated and non-redundant transcription factor (TF) binding profiles from six different taxonomic groups.

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BRAIN-MAGNET, a convolutional neural network trained on 148,198 functionally tested non-coding regulatory elements, predicts enhancer activity directly from DNA sequence and identifies nucleotides ess...

Subtle genomic variations between humans and Neanderthals provide clues to how DNA shapes our facial features.

A new method for quantitative assessment of altered regulatory potential of human enhancers bearing disease-associated mutations using live imaging in zebrafish embryos.