Replication stress underlies many genomic alterations in cancer cells. In this issue of Developmental Cell, Benedict et al. show that WAPL-dependent cohesin removal is needed to restart DNA synthesis at stalled forks and promote survival following replication stress, uncovering an unexpected link between stress and sister chromatid cohesion loss.

Lamin proteins not only form the nuclear lamina, but some are also found in the nuclear interior. In this issue of Developmental Cell, Ikegami et al. describe that phosphorylated Lamin C in the nuclear interior interacts with enhancer-like elements and link this to deregulated transcription in progeria.

Cell stress often triggers inflammation as a protective response to tissue damage or infection. In this issue of Developmental Cell, Sullivan et al. (2020) reveal an unexpected role for TRAIL receptors in ER-stress-induced inflammation.

Notch signaling is a major regulator of pancreas development, yet how it precisely controls pancreatic cell fates has remained obscure. Seymour et al. (2020) use sophisticated Notch- based genetic tools to uncover highly context- and temporally-specific roles for DLL1, JAG1, and HES1 in regulating pancreatic progenitor cell growth and specification.

The centriole, or basal body, is the center of attachment between the sperm head and tail. While the distal end of the centriole templates the cilia, the proximal end associates with the nucleus. Using Drosophila, we identify a centriole-centric mechanism that ensures proper proximal end docking to the nucleus. This mechanism relies on the restriction of pericentrin-like protein (PLP) and the pericentriolar

Cells in our body have to divide within a defined tissue space, which in tumors is more restricted than in normal tissue. In this issue of Developmental Cell, Matthews et al. (2020) reveal that oncogenic RasV12-mediated cell rounding and cortical stiffening promote cell division under confined conditions that are similar to those in tumors.

Cancer cells need to acquire specific molecular traits in order to spread to distant organs. In this issue of Developmental Cell, Marsh et al. show that autophagy restricts the outgrowth of breast cancer metastases in contrast to its impact on primary tumor progression.

Crosstalk between signaling networks can help coordinate diverse cellular functions. In this issue of Developmental Cell, Tyra et al. identify connections between the cell-growth-promoting transcription factor YAP/Yorkie and the autophagy-regulating kinase Ulk1/Atg1.

How lung epithelium and endothelium co-develop to maintain structural integrity of alveoli remains unclear. In this issue of Developmental Cell, Ellis et al. define how epithelial Vegfa directs development of a distinct endothelial cell population that ultimately plays a critical role in ensuring appropriate alveolar septation during alveologenesis.

Stress has long been associated with hair graying, yet there is little evidence to substantiate this claim. In a recent issue of Nature, Zhang et al. (2020) show that stress induces the release of noradrenaline from sympathetic nerves, which depletes the stem cells that give hair their color.

Motile cells have developed a variety of migration modes relying on diverse traction-force-generation mechanisms. Before the behavior of intracellular components could be easily imaged, cell movements were mostly classified by different types of cellular shape dynamics. Indeed, even though some types of cells move without any significant change in shape, most cell propulsion mechanisms rely on global

Optogenetic perturbations, live imaging, and time-resolved ChIP-seq assays in Drosophila embryos were used to dissect the ERK-dependent control of the HMG-box repressor Capicua (Cic), which plays critical roles in development and is deregulated in human spinocerebellar ataxia and cancers. We established that Cic target genes are activated before significant downregulation of nuclear localization of

Many eukaryotic cells distribute their intracellular components asymmetrically through regulated active transport driven by molecular motors along microtubule tracks. While intrinsic and extrinsic regulation of motor activity exists, what governs the overall distribution of activated motor-cargo complexes within cells remains unclear. Here, we utilize in vitro reconstitution of purified motor proteins

Bud tip progenitor cells give rise to all murine lung epithelial lineages and have been described in the developing human lung; however, the mechanisms controlling human bud tip differentiation into specific lineages are unclear. Here, we used homogeneous human bud tip organoid cultures and identified SMAD signaling as a key regulator of the bud tip-to-airway transition. SMAD induction led to the differentiation

Eukaryotic genomes are organized within the nucleus through interactions with inner nuclear membrane (INM) proteins. How chromatin tethering to the INM is controlled in interphase and how this process contributes to subsequent mitotic nuclear envelope (NE) remodeling remains unclear. We have probed these fundamental questions using the fission yeast Schizosaccharomyces japonicus, which breaks and reforms

Phosphoinositides are signaling lipids that recruit effector proteins to membranes. Shin et al. show that a glucose-starvation-induced drop in cytosolic pH alters the protonation state of the phosphoinositide PI4P, resulting in dissociation of its effector Osh1 from the trans-Golgi network membrane and metabolic regulation of lipid and protein sorting.

The capacity to undergo meiosis defines vertebrate germ cells, yet mechanisms driving initiation of this specialized process are largely undefined. In this issue of Developmental Cell,Ishiguro et al. (2020) identified the transcription factor MEIOSIN as a gatekeeper of meiotic initiation in both male and female germ cells.

Male fertility is driven by spermatogonial stem cells (SSCs) that self-renew while also giving rise to differentiating spermatogonia. Spermatogonial transitions are accompanied by a shift in gene expression, however, whether equivalent changes in metabolism occur remains unexplored. In this review, we mined recently published scRNA-seq databases from mouse and human testes to compare expression profiles

High levels of cancer aneuploidy are frequently associated with poor prognosis. To examine the relationship between aneuploidy and cancer progression, we analyzed a series of congenic cell lines that harbor single extra chromosomes. We found that across 13 different trisomic cell lines, 12 trisomies suppressed invasiveness or were largely neutral, while a single trisomy increased metastatic behavior

Drosophila neural progenitors require the transcriptional repressor Prospero to promptly establish the neuronal fate of their daughter cells to avoid tumorigenesis. In this issue of Developmental Cell, Liu et al. (2020) find that Prospero is mitotically implanted and forms liquid-like droplets mediating HP1a condensation to permanently repress its targets.

Spatial repositioning of genes in nuclear space has been extensively linked to regulation of gene expression, but the mechanisms behind this directed movement have remained uncertain. In this issue of Developmental Cell, Wang et al. (2020) describe a nuclear actin-myosin-based pathway driving the movement of activated genes to the nuclear periphery.

Boundary formation between nascent tissues prevents cell mixing, powering morphogenesis. In this issue of Developmental Cell, Sidor et al. (2020) describe a novel mechanism whereby the homophilic adhesion protein Crumbs regulates planar-polarized assembly of actomyosin cables at tissue boundaries by affecting dynamics of membrane recruitment of the myosin regulator Rho-kinase.

Chromosomes containing two centromeres (dicentrics) trigger chromosome instability that is avoided by the enigmatic process of centromere inactivation. In this issue of Developmental Cell, Palladino et al. (2020) combine in vivo chromosome engineering and Drosophila genetics to assess consequences of de novo centromere formation and clarify models of centromere inactivation.

TGF-β is long known to require Ras activation to induce EMT. In a recent issue of Nature, Massagué and colleagues (Su et al., 2020) identify RAS-responsive element binding protein 1 (RREB1) as a critical integrator of TGF-β and Ras signals during both developmental and cancer EMT programs.

We summarize recent work illuminating how cerebrospinal fluid (CSF) regulates brain function. More than a protective fluid cushion and sink for waste, the CSF is an integral CNS component with dynamic and diverse roles emerging in parallel with the developing CNS. This review examines the current understanding about early CSF and its maturation and roles during CNS development and discusses open questions

Pulsed actomyosin contractions drive morphogenetic processes, but how cyclic frequencies and amplitudes of contractions are tuned to achieve processive shrinking of cell surfaces remains unclear. In this issue of Developmental Cell, Cavanaugh et al. (2020) use optogenetics and biophysical modeling to demonstrate how cells respond to different oscillatory force profiles.

Plant cells use polarity cues to confine membrane proteins to specific localizations. In this issue of Developmental Cell, Marhava et al. (2020) describe a biochemical feedforward mechanism that reinforces polar protein localization and regulates membrane composition and endocytosis.

Embryonic diapause is the reversible arrest in development of mammalian embryos at the blastocyst stage. In this issue of Developmental Cell, Hussein et al. (2020) reveal that alternative splicing of Lkb1 is essential for diapause to persist and find the elevation of glycolytic and lipolytic pathways that were previously considered dormant.

We explored the potential for autophagy to regulate budding yeast meiosis. Following pre-meiotic DNA replication, we blocked autophagy by chemical inhibition of Atg1 kinase or engineered degradation of Atg14 and observed homologous chromosome segregation followed by sister chromatid separation; cells then underwent additional rounds of spindle formation and disassembly without DNA re-replication, leading