Most metazoan cells entering mitosis undergo characteristic rounding, which is important for accurate spindle positioning and chromosome separation. Rounding is driven by contractile tension generated by myosin motors in the sub-membranous actin cortex. Recent studies highlight that alongside myosin activity, cortical actin organization is a key regulator of cortex tension. Yet, how mitotic actin organization is controlled remains poorly understood. To address this, we characterized the F-actin interactome in spread interphase and round mitotic cells. Using super-resolution microscopy, we then screened for regulators of cortex architecture and identified the intermediate filament vimentin and the actin-vimentin linker plectin as unexpected candidates. We found that vimentin is recruited to the mitotic cortex in a plectin-dependent manner. We then showed that cortical vimentin controls actin network organization and mechanics in mitosis and is required for successful cell division in confinement. Together, our study highlights crucial interactions between cytoskeletal networks during cell division.

Dynamic regulation of lysosomes allows them to play key roles in cell and tissue homeostasis. In this issue of Developmental Cell, Miao et al. find that a novel transcriptional pathway triggered by loss of cell adhesion activates lysosomes in C. elegans epidermis during developmental remodeling of the cuticle.

Germ cells carry genetic information to the next generation, necessitating special attention to their genome maintenance. Two new studies in this issue of Developmental Cell (Bhargava et al., 2020, Dokshin et al., 2020) reveal an essential function of germ cell-specific protein GCNA in the genome maintenance of germ cells.

During development, neurons form growth cones and neurites, but later reduce these activities to maintain a stable architecture. In this issue of Developmental Cell, LaBella et al. demonstrate that CK1δ plays a key role in winding down developmental processes exclusively by regulating poly(A) site choice to promote giant Ankyrin isoform expression.

Legumes, a subset of flowering plants, form root nodules in symbiosis with nitrogen-fixing bacteria. The regulatory network controlling nodule formation has remained mysterious. In a recent issue of Science, Soyano et al. (2019) demonstrate that co-option of an existing lateral root developmental program is used in Lotus for nodule organogenesis.

Epithelial remodeling involves ratcheting behavior whereby periodic contractility produces transient changes in cell-cell contact lengths, which stabilize to produce lasting morphogenetic changes. Pulsatile RhoA activity is thought to underlie morphogenetic ratchets, but how RhoA governs transient changes in junction length, and how these changes are rectified to produce irreversible deformation, remains poorly understood. Here, we use optogenetics to characterize responses to pulsatile RhoA in model epithelium. Short RhoA pulses drive reversible junction contractions, while longer pulses produce irreversible junction length changes that saturate with prolonged pulse durations. Using an enhanced vertex model, we show this is explained by two effects: thresholded tension remodeling and continuous strain relaxation. Our model predicts that structuring RhoA into multiple pulses overcomes the saturation of contractility and confirms this experimentally. Junction remodeling also requires formin-mediated E-cadherin clustering and dynamin-dependent endocytosis. Thus, irreversible junction deformations are regulated by RhoA-mediated contractility, membrane trafficking, and adhesion receptor remodeling.

Myelination in the CNS requires oligodendrocytes to first select correct axonal targets and then extend their membranes around and along these axons. In this issue of Developmental Cell, Klingseisen et al. (2019) find that the adhesion protein Neurofascin is required in oligodendrocytes for both target selection and myelin growth.

Primary cilia function as cellular signaling hubs, integrating multiple signaling pathways. Patients with the ciliopathy Joubert syndrome have been suggested to have axonal tract defects. In this issue of Developmental Cell, Guo et al. (2019) demonstrate a ciliary signaling requirement for axonal tract development and connectivity through dysregulated PI3K/AKT/ACIII signaling.

Seipin is an ER protein important for the assembly of cytoplasmic lipid droplets. In this issue of Developmental Cell, Chung et al. (2019) show that a stable seipin-binding protein, LDAF1/promethin, functions with seipin by attracting triacylglycerol and then allowing this lipid to accumulate and partition into nascent droplets.

In this issue of Developmental Cell, Niwayama et al. (2019) describe a model in which cell polarity and cell shape compete to determine the orientation of cell division in the pre-implantation mouse embryo. This model explains how simple cell-intrinsic rules lead to robust tissue-level morphogenesis and lineage segregation.

Ferroptosis causes clinically relevant amounts of necrosis during the course of heart attacks and acute kidney injury. However, ferroptosis is still a very young research field. In this issue of Developmental Cell, Brown et al. describe the pentaspan membrane glycoprotein prominin-2 as a novel endogenous ferroptosis inhibitor.

The actin remodeling factor N-WASP is best known as an Arp2/3 complex activator in processes like endocytosis, extracellular matrix degradation, and host-pathogen interaction. In this issue of Developmental Cell, Juin et al. establish a novel trafficking function for N-WASP in driving lysophosphatidic acid-dependent chemotaxis and metastasis of pancreatic cancer cells.

Carcinoma cells often acquire mobility and invasiveness by undergoing epithelial-to-mesenchymal transition, and yet most metastatic lesions remain epithelial in nature. Recently, in Nature, Padmanaban et al. (2019) demonstrated that the quintessential epithelial marker E-cadherin promotes metastasis of invasive ductal breast carcinoma by enhancing the survival of tumor cells.

Inconsistent activity limits the use of CRISPR-Cas9 in zebrafish. We show supernumerary guanine nucleotides at the 5′ ends of single guide RNAs (sgRNAs) account for diminished CRISPR-Cas9 activity in zebrafish embryos. Genomic sequences can be targeted consistently with extremely high efficiency using Cas9 ribonucleoproteins (RNPs) containing either a sgRNA molecule or a synthetic crRNA:tracrRNA duplex that perfectly matches the protospacer target site. Following injection of zebrafish eggs with such RNPs, virtually every copy of a targeted locus harbors an induced indel mutation. Loss of gene function is often complete, as F0 embryos closely resemble true null mutants without detectable non-specific effects. Mosaicism is sufficiently low in F0 embryos that cell non-autonomous gene functions can be probed effectively and redundant activities of genes can be uncovered when two genes are targeted simultaneously. Finally, heritable deletion mutations of at least 50 kbp can be readily induced using pairs of duplex guide RNPs targeted to a single chromosome.

In this issue of Developmental Cell, Ransick et al. (2019) provide a comprehensive anatomically guided single-cell dataset from adult mouse kidney, representing the most detailed analysis of the cellular heterogeneity and lineage relationship of cells in the adult mouse kidney published to date.

Homologous chromosomes pair in somatic cells in Drosophila, but how this occurs is poorly understood. In this issue of Developmental Cell, Viets et al. (2019) show that proteins and chromatin structure mediate pairing and argue against a DNA sequence-based mechanism.

Multiple stem cells maintain and repair tissues, yet how they communicate is not well understood. In this issue of Developmental Cell, Veniaminova et al. (2019) report that each sebaceous gland is maintained by local stem cells and that Notch signaling regulates multiple aspects of their function, revealing tissue homeostasis mechanisms.