In this issue of Developmental Cell, Li et al. develop a novel lineage tracing system to record EMT activity during lung metastasis of mammary tumors. Using EMT-tracer mouse models, they reveal that N-cadherin is transiently expressed by most metastasis-initiating cells and demonstrate its functional importance during the metastatic cascade.

In this issue of Developmental Cell, Trushko et al. (2020) develop a bottom-up approach to understand the physics underlying confined epithelial monolayer folding. Investigating this process is currently unattainable in vivo but is essential to our understanding of tissue formation from the gastrulating blastula to the developing nervous system.

Lipidated morphogens can spread within tissues to regulate cell fate during development or tissue repair. How these insoluble molecules reach distant target cells remains unclear. Reporting in Nature, McGough et al. (2020) reveal the secret of how the cell-surface proteoglycan Dally-like-protein (Dlp) promotes long-range signaling of the palmitoylated morphogen Wingless.

Teeth are attached to alveolar bone by the periodontal ligament (PDL), which contains stem cells supporting tissue turnover. Here, we identified Gli1+ cells in adult mouse molar PDL as multi-potential stem cells (PDLSCs) giving rise to PDL, alveolar bone, and cementum. They support periodontium tissue turnover and injury repair. Gli1+ PDLSCs are surrounding the neurovascular bundle and more enriched

Hallmark mutations in WNT and SHH medulloblastoma are usually distinct, but DDX3X is often mutated in both subgroups. In this issue of Developmental Cell, Patmore et al. identify Ddx3x as essential for hindbrain patterning, cell fate determination, and as a tumor suppressor gene that restricts cell lineage progression in tumorigenesis.

In this issue of Developmental Cell, Xie et al. show that in cystic fibrosis, airway gland mucus gels form under conditions of high acidity and protein concentration. This causes them to be unusually stiff. This abnormal rheology cannot be corrected by changing pH or calcium levels in the bathing medium.

The mechanisms that govern cell interactions during organ formation are not fully understood. In this issue of Developmental Cell, Miao et al. demonstrate a channel-independent role for gap junction proteins in the establishment of contacts between three cell types that build up the micropyle during oocyte development in Drosophila.

Damage to the intestinal stem cell niche can result from mechanical stress, infections, chronic inflammation or cytotoxic therapies. Progenitor cells can compensate for insults to the stem cell population through dedifferentiation. The microenvironment modulates this regenerative response by influencing the activity of signaling pathways, including Wnt, Notch, and YAP/TAZ. For instance, mesenchymal

The extracellular matrix (ECM) plays a major role in cancer progression through its increased deposition and alignment. In this issue of Developmental Cell, Fattet et al. reveal a pathway in which ECM stiffness promotes EPHA2/LYN complex activation, leading to TWIST1 nuclear localization and triggering EMT in breast cancer.

A fully functional placenta is critical for a successful pregnancy. In this issue of Developmental Cell, Singh et al. reveal that excessive placental DNA damage in murine models for Cornelia de Lange syndrome results in an inefficient and senescent placenta that impairs embryonic development.

In this issue of Developmental Cell, Mukherjee et al. (2020) investigate control of nuclear growth by live imaging of early embryogenesis, perturbations of blastomere dimensions, and reconstitution in vitro. The authors uncover new mechanisms of nuclear size scaling by the amount of inherited perinuclear ER and duration of interphase.

Mechanical cues from the extracellular matrix (ECM) regulate various cellular processes via distinct mechanotransduction pathways. In breast cancer, increased ECM stiffness promotes epithelial-to-mesenchymal transition (EMT), cell invasion, and metastasis. Here, we identify a mechanosensitive EPHA2/LYN protein complex regulating EMT and metastasis in response to increasing ECM stiffness during tumor

How are diverse regulatory strategies integrated to impose appropriately patterned gene expression that underlie in vivo phenotypes? Here, we reveal how coordinated miRNA regulation and neural-specific alternative polyadenylation (APA) of a single locus controls complex behaviors. Our entry was the unexpected observation that deletion of Bithorax complex (BX-C) miRNAs converts virgin female flies into

Formation of biomolecular condensates that are not enclosed by membranes via liquid-liquid phase separation (LLPS) is a general strategy that cells adopt to organize membraneless subcellular compartments for diverse functions. Neurons are highly polarized with elaborate branching and functional compartmentalization of their neurites, thus, raising additional demand for the proper subcellular localization

In eukaryotic cells, various membrane-bound organelles compartmentalize diverse cellular activities in a spatially and temporally controlled manner. Numerous membraneless organelles assembled via liquid-liquid phase separation (LLPS), known as condensates, also facilitate compartmentalization of cellular functions. Emerging evidence shows that these two organelle types interact in many biological processes

Posterior fossa type A (PFA) ependymoma is a lethal pediatric brain tumor proposed to be driven solely by epigenetic deregulation. Michealraj et al. (2020) demonstrate that hypoxia reprograms PFA metabolism and, subsequently, the epigenome toward H3K27 hypomethylation, mirroring transcriptional and metabolic signatures of gliogenic progenitors involved in embryonal hindbrain development.

Blood vessels are an essential interface between the circulation and tissue that deploy signaling molecules (angiocrines) for organ development, homeostasis, and repair. In a recent issue of Cell Metabolism, Zhang et al. (2020) identify lactate as an endothelial-derived signal promoting ischemic muscle regeneration, establishing metabolites as a new angiocrine class.

A major trigger of adult β-cell insulin secretion is glucose. In a recent issue of Cell Metabolism, Helman and colleagues show that in fetuses insulin secretion depends on the activation of mTOR by amino acids and that reducing amino acids promotes maturation of β-cells derived from pluripotent stem cells.

Metabolites affect cell growth in two different ways. First, they serve as building blocks for biomass accumulation. Second, metabolites regulate the activity of growth-relevant signaling pathways. They do so in part by covalently attaching to proteins, thereby generating post-translational modifications (PTMs) that affect protein function, the focus of this Perspective. Recent advances in mass spectrometry

Membrane lipids are often viewed as passive building blocks of the endomembrane system. However, mounting evidence suggests that sphingolipids, sterols, and phospholipids are specifically targeted by developmental pathways, notably hormones, in a cell- or tissue-specific manner to regulate plant growth and development. Targeted modifications of lipid homeostasis may act as a way to execute a defined