Developmental biology and regeneration

Microglia cells in the brain regulate immune responses, but in ageing can negatively affect brain function. Here the authors show that the chronic presence of type I interferon in aged mouse brain impedes cognitive ability by altering microglia transcriptome and limiting Mef2C, a microglia ‘off’ signal.

Asymmetric nuclear positioning in the fruit fly oocyte is essential for the correct localization of axis determinants. Here, the authors show that different microtubule-dependent mechanisms contribute to nuclear transport and ensure the robustness of nuclear positioning.

Neural crest cells arise within the central nervous system, then migrate and contribute to a variety of cell types. Here, the authors use multiplex transcript analysis at single cell  resolution to define neural crest and neural subpopulations within the avian neural tube, including a neural crest stem cell niche.

A better understanding of the earliest stages of human cancer formation can enable future improvements in early detection, diagnosis and treatment. In this review, the authors summarize the methods enablingde novotumorigenesis protocols to be applied to human cells and the insights derived from them to date, as well as the exciting and relevant technical developments anticipated to extend even further the utility of these strategies.

The evolution of germ cell specification by maternal germ plasm has been proposed to accelerate vertebrate protein evolution by liberating selective constraints. Whittle and Extavour analyse global rates of protein evolution and find no support for this hypothesis in vertebrates or invertebrates.

“Variation in the noncoding regulatory sequences in the genome plays important roles in human disease and evolution. Here, the authors use F1 mouse hybrids to shed light on the regulatory mechanisms mediating transcription factor binding, chromatin state and gene expression in mammalian cells.”

Keratin 16 is an epithelial protein highly expressed at pressure bearing sites and during wound healing and cancer. Here the authors show that K16 interacts with the inactive protease Rhbdf2, associated with Tylosis with oesophageal cancer, and that this interaction drives increased keratinocyte proliferation.

Lateral root development is dependent on precise control of the distribution of the plant hormone auxin. Here Chen et al. propose the transcription factors ARF7 and FLP participate in a feed forward motif to mediate expression of the auxin transporter PIN3and consequently regulate lateral root development.

In the mouse embryo, anterior-posterior polarity is established by distal visceral endoderm (DVE) at embryonic day 5.5 but how this arises is unclear. Here, the authors show that expression of Lefty1 earlier can define DVE, and that future DVE cells are selected by Nodal signalling and stochasticity.

X-chromosome inactivation is reversed in the mouse inner cell mass (ICM) through a mechanism that is not fully understood. Here, the authors investigate this process and characterize the contributions of the epigenetic landscape and transcription factors in X-linked gene reactivation dynamics.

Xist RNA is required for X chromosome inactivation but it is not well understood how Xist silences some regions more efficiently than others. Here, the authors induce ectopic Xist expression from multiple different X-linked and autosomal loci in cells to explore Xist function.

Although protein tyrosine kinases are being explored as antifibrotic agents for the treatment of systemic sclerosis, little is known about the function of counteractive protein tyrosine phosphatases in this context. Here, the authors show that PTP4A1 is highly expressed by fibroblasts from patients with systemic sclerosis and promotes TGFβ activity via SRC–ERK–SMAD3 signaling.

Human WNT10A mutations are associated with dental defects and adult onset ectodermal dysplasia. Xuet al. show that WNT10A-activated ß-catenin plays dual roles in adult epithelial progenitor proliferation and differentiation by complexing with KLF4 in differentiating, but not proliferating, cells.

The use of stem cell-derived cardiomyocytes for heart repair is hampered by their immature structural and contractile properties that may cause arrhythmia. Here, Eng et al.show that electrical conditioning of human cardiomyocytes in 3D culture can enhance connectivity and provide resistance to arrhythmia.

mTOR regulates cell growth via a protein complex including mTORC1 and mTORC2, but their role in skin morphogenesis is unclear. Here, the authors delete mTORC1 and mTORC2 from the epidermis and see epidermal deficiencies but both mTORCs play distinct roles in skin morphogenesis.

The TOR and insulin/IGF signalling (IIS) network are central responses to wound healing. Here the authors develop a technique of live imaging of laser-induced epidermal wounds to flies and show that TOR and IIS are independently required for wound healing, which may have implications for diabetic wound healing and its treatment.

Retinoic acid (RA) regulates the maintenance of somitogenesis symmetry. Here, the authors use a proteomic approach to identify a protein complex of Wdr5, Hdac1, Hdac2 that act together with RA and coactivator Rere/Atrophin2 and a histone methyltransferase Ehmt2 to regulate embryonic symmetry.

The role of stem/progenitor cell populations in mammary gland morphogenesis is not well understood. Here, the authors show that a transcriptional repressor, Blimp1, is expressed in a rare luminal stem cell population, which contribute to duct formation, and survive multiple rounds of pregnancy and involution.

Mouse digit patterning is controlled by a Turing network of Bmp, Sox9, and Wnt. Here, Onimaru et al. show that fin patterning in the catshark, Scyliorhinus canicula, is controlled by the same network with a different spatial organization; thus, the Turing network is deeply conserved in limb development.

Biomphalaria glabrata is a fresh water snail that acts as a host for trematode Schistosoma mansoni that causes intestinal infection in human. This work describes the genome and transcriptome analyses from 12 different tissues of B glabrata, and identify genes for snail behavior and evolution.

Chemical screens can identify small molecules that affect biological development, with potential therapeutic value. Here, the authors use a modular approach in a screen in zebrafish embryos, varying concentration, genotype and timing to target segmentation disorders, birth defects that affect the spinal column.

The mechanistic coupling of cell growth and cell cycle control with cell size regulation in tissues is not well understood. Here, the authors show that within the shoot apical meristem of Arabidopsis cell size depends on developmental stage, genotype and environmental signals; however cell growth and cell division are cell-autonomously coordinated.

Deep sequencing technologies allow for the investigation of clonal evolution in human cancers. Here the authors, combining sequencing data from human skin with mathematical modelling and simulations, suggest that the spatial context of a mutation with respect to other mutant clones may lead to differential clonal evolution.

Individual human epidermal cells differ in their self-renewal ability. Here the authors perform genome-wide pooled RNAi screens to uncover the molecular basis for this heterogeneity, and identify genes conferring a clonal growth advantage on normal and neoplastic human epidermal cells.

Commitment to different fates by differentiating pluripotent cells depends upon integration of external and internal signals. Here the authors analyse the entry of mouse embryonic stem cells into retinoic acid-mediated differentiation using single cell transcriptomics with high temporal resolution.

Early in human embryonic development, it is unclear how amniotic sac formation is regulated. Here, the authors use a human pluripotent stem cell-based model, termed the post-implantation amniotic sac embryoid, to recapitulate early embryogenic events of human amniotic sac development.

The diet consumed during development can have long-lasting effects on adult physiology. Here, the authors show that developmental undernutrition in Drosophila extends lifespan by inhibiting the production of toxic lipids, called autotoxins, on the adult body surface.

The molecular trigger that establishes cell polarity in the mammalian embryo is unclear. Here, the authors show that de novo polarisation of the mouse embryo at the 8-cell stage is directed by Phospholipase C and Protein kinase C and occurs in two phases: polarisation of actomyosin followed by the Par complex.

The role of mechanical signals in early development are not fully understood. Here, the authors use the simplicity of early killifish embryos to show that tension arising from extra-embryonic epithelial expansion directs the spreading of mesenchymal-like embryonic cells during early morphogenesis.

In the Drosophila ovary, it is unclear how signalling from the stem cell niche regulates follicle precursor cell fate/differentiation. Here, the authors use quantitative microscopy to define the role of Wnt, Hedgehog and Notch signalling in progenitor cells, showing regulation of cell fate and differentiation.

The mechanisms that cause different cells to segregate into distinct tissues are unclear. Here the authors show in Xenopus that formation of a boundary between two tissues is driven by local tension along the interface rather than by global differences in adhesion or cortical contractility.

Long noncoding RNAs (lncRNAs) are key regulators of lineage specification during development. Here, the authors investigate remodeling of enhancers and regulation of the lncRNA transcriptome during mesendoderm specification, and identify a pluripotent stage-specific transcribed enhancer controlling adoption of the mesendodermal cell fate.

Derivation of human induced pluripotent stem cells (hiPSCs) produces primed hiPSCs that can in turn be converted to naive hiPSCs. Here, the authors directly reprogram somatic cells to form both naive and primed isogenic hiPSCs and confirm the similarity of naive hiPSCs to their in vivo counterparts.

Embryonic stem cell pluripotency depends upon precise regulation by a core transcription network. Here the authors show that polyglutamylation mediated stabilization of the transcription factor Klf4 by TTLL1 and TTLL4 promotes reprogramming, pluripotency and preimplantation embryonic development.

The neuroectoderm is patterned in a rostral-caudal axis in the embryo but how positional information is interpreted, is unclear. Here, the authors show that in mouse 3D embryonic stem cell cultures, there is self-patterning that depends on sequential activation of localised Fgf then Wnt signalling.

Advanced maternal age has been associated with lower reproductive success and higher risk of pregnancy complications. Here the authors show that maternal ageing-related embryonic abnormalities in mouse are caused by decidualisation and placentation defects that can be rescued by transferring the embryo from an old to a young uterus.

The pancreas arises from a small population of cells but how individual cells contribute to organ formation is unclear. Here, the authors deconstruct pancreas organogenesis into clonal units, showing that single progenitors give rise to heterogeneous multi-lineage and endocrinogenic single-lineage clones.

Cell fusion regulates several physiological events, for example, fusion of myoblasts in skeletal muscle formation, but it is unclear if this process occurs in the heart. Here, the authors use transgenic reporters in zebrafish to show transient cardiomyocyte fusion, modulating cardiac development and function.

Priming of the adult mouse heart with Tβ4 activates dormant epicardium-derived cells to aid repair of injured myocardium. Here, Vieiraet al. explain this process and show that Tβ4 binds a chromatin remodeller BRG1 and activates Wt1, the key regulator of epicardial epithelial-to-mesenchymal transformation, by altering the epigenetic landscape of the Wt1 locus.

Cellular fusion is fundamental for skeletal muscle development. Here the authors show that myomerger is expressed in myoblasts, is essential for myoblast fusion in mice, and in co-operation with myomaker confers fusogenic ability to non-fusogenic cells.

Extracellular matrix (ECM) remodelling is thought to have effects on muscle stem cells that support muscle homeostasis. Here the authors show ECM remodeling controls satellite cell self-renewal through deposition of laminin-α1 into the satellite cell niche.

The generation of functional skeletal muscle tissue from human pluripotent stem cells has not been reported. Here, the authors describe engineering of contractile skeletal muscle bundles in culture, which become vascularized and maintain functionality when transplanted into mice.

How neurons and neuronal activity regulate astrocyte functions is poorly understood. Haselet al. identify two large groups of astrocytic genes that are regulated by neuronal contact and synaptic activity respectively, with distinct roles in astrocytic function; interestingly, many of these genes are dysregulated in neurodegeneration.

Planarian regenerative mechanisms suggest that muscle has an instructive role in patterning. Here, the authors show that muscle is also responsible for regenerative patterning information in an early-branching bilaterian, Hofstenia miamia, dating this back to the dawn of the Bilateria, over 550 million years ago.

Some wounds trigger regeneration, while others simply heal but how this is regulated is unclear. Here, by manipulating ERK and Wnt signalling pathways, the authors create headless planarians and finless zebrafish and show that wounds that normally only trigger wound healing can activate regeneration of heads and bones.

Common mechanisms underlie organ regeneration, but it is unclear if the same regulatory elements are activated in distinct cells, such as cardiomyocytes and fibroblasts. Here, the authors identify actgfa upstream sequence, called careg, induced by TGFb/Activin during zebrafish heart and fin regeneration.

Following spinal injury in zebrafish, non-neural cells establish an extracellular matrix to promote axon re-growth but how this is regulated is unclear. Here, the authors show that Wnt/β-catenin signaling in fibroblast-like cells at a lesion activates axon re-growth via deposition of Collagen XII.

In response to gut epithelial damage,Drosophilastem cells proliferate to produce large polyploid enterocytes (EC), which comprise the bulk of the epithelium. Here, the authors show that stress-dependent EGFR/MAP kinase signalling drives both endoreplication and cell growth in newborn ECs.

Higher-order chromatin organization regulates the expression of transcriptional programs that control cell function. Here, the authors show that chromatin interaction profiles and nuclear positions at developmental gene loci differ between human somatic and pluripotent stem cells.

Haematopoietic stem cell (HSC) self-renewal is not sufficiently understood to recapitulate in vitro. Here, the authors generate gene signature and cell cycle hallmarks of single murine HSCs, and use identified endothelial receptors Esam and JamC as substrates to enhance HSC growth in engineered niches.

Senescence has been suggested as causing biliary cholangiopathies but how this is regulated is unclear. Here, the authors generate a mouse model of biliary senescence by deleting Mdm2 in bile ducts and show that inhibiting TGFβ limits senescence-dependent aggravation of cholangiopathies.