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Regulation of Nematostella neural progenitors by SoxB, Notch and bHLH genes

Notch signalling, SoxB and Group A bHLH ‘proneural’ genes are conserved regulators of the neurogenic program in many bilaterians. However, the ancestry of their functions and interactions is not well understood. We address this question in the sea anemone Nematostella vectensis, a representative of the Cnidaria, the sister clade to the Bilateria. It has previously been found that ...

Arabidopsis HECATE genes function in phytohormone control during gynoecium development

The fruit, which develops from the fertilised gynoecium formed in the innermost whorl of the flower, is the reproductive organ and one of the most complex structures of an angiosperm plant. Phytohormones play important roles during flower and fruit patterning, morphogenesis and growth, and there is emerging evidence for a cross-talk between different classes of plant hormones ...

Coordinate post-transcriptional repression of Dpp-dependent transcription factors attenuates signal range during development

Precise control of the range of signalling molecule action is crucial for correct cell fate patterning during development. For example, Drosophila ovarian germline stem cells (GSCs) are maintained by exquisitely short-range BMP signalling from the niche. In the absence of BMP signalling, one GSC daughter differentiates into a cystoblast (CB) and this fate is stabilised by Brain ...

Cytoophidium assembly reflects upregulation of IMPDH activity

Cytidine triphosphate synthase (CTPS) and inosine monophosphate dehydrogenase (IMPDH) (both of which have two isoforms) can form fiber-like subcellular structures termed ‘cytoophidia’ under certain circumstances in mammalian cells. Although it has been shown that filamentation of CTPS downregulates its activity by disturbing conformational changes, the activity of IMPDH within ...

Low levels of endogenous or X-ray-induced DNA double-strand breaks activate apoptosis in adult neural stem cells

The embryonic neural stem cell compartment is characterised by rapid proliferation from embryonic day (E)11 to E16.5, high endogenous DNA double-strand break (DSB) formation and sensitive activation of apoptosis. Here, we ask whether DSBs arise in the adult neural stem cell compartments, the sub-ventricular zone (SVZ) of the lateral ventricles and the sub-granular zone (SGZ) of the ...

mRNA encoding Sec61β, a tail-anchored protein, is localized on the endoplasmic reticulum

Although one pathway for the post-translational targeting of tail-anchored proteins to the endoplasmic reticulum (ER) has been well defined, it is unclear whether additional pathways exist. Here, we provide evidence that a subset of mRNAs encoding tail-anchored proteins, including Sec61β and nesprin-2, is partially localized to the surface of the ER in mammalian cells. In ...

A Chlamydia effector recruits CEP170 to reprogram host microtubule organization

The obligate intracellular bacterial pathogen Chlamydia trachomatis deploys virulence effectors to subvert host cell functions enabling its replication within a specialized membrane-bound compartment termed an inclusion. The control of the host cytoskeleton is crucial for Chlamydia uptake, inclusion biogenesis and cell exit. Here, we demonstrate how a Chlamydia effector rearranges ...

Enabling research with human embryonic and fetal tissue resources

Congenital anomalies are a significant burden on human health. Understanding the developmental origins of such anomalies is key to developing potential therapies. The Human Developmental Biology Resource (HDBR), based in London and Newcastle, UK, was established to provide embryonic and fetal material for a variety of human studies ranging from single gene expression analysis to ...

The advancement of human pluripotent stem cell-derived therapies into the clinic

Human pluripotent stem cells (hPSCs) offer many potential applications for drug screening and ‘disease in a dish’ assay capabilities. However, a more ambitious goal is to develop cell therapeutics using hPSCs to generate and replace somatic cells that are lost as a result of disease or injury. This Spotlight article will describe the state of progress of some of the hPSC-derived ...

When rejuvenation is a problem: challenges of modeling late-onset neurodegenerative disease

In contrast to the successful modeling of early-onset disorders using patient-specific cells, modeling of late-onset neurodegenerative diseases such as Parkinson's disease remains a challenge. This might be related to the often ignored fact that current induced pluripotent stem cell (iPSC) differentiation protocols yield cells that typically show the behavior of fetal stage cells. ...

The pluripotent state in mouse and human

In the mouse, naïve pluripotent stem cells (PSCs) are thought to represent the cell culture equivalent of the late epiblast in the pre-implantation embryo, with which they share a unique defining set of features. Recent studies have focused on the identification and propagation of a similar cell state in human. Although the capture of an exact human equivalent of the mouse naïve ...

Genomic approaches to studying human-specific developmental traits

Changes in developmental regulatory programs drive both disease and phenotypic differences among species. Linking human-specific traits to alterations in development is challenging, because we have lacked the tools to assay and manipulate regulatory networks in human and primate embryonic cells. This field was transformed by the sequencing of hundreds of genomes – human and ...

Modeling mouse and human development using organoid cultures

In vitro three-dimensional (3D) cultures are emerging as novel systems with which to study tissue development, organogenesis and stem cell behavior ex vivo. When grown in a 3D environment, embryonic stem cells (ESCs) self-organize into organoids and acquire the right tissue patterning to develop into several endoderm- and ectoderm-derived tissues, mimicking their in vivo ...

Human pancreas development

A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss ...

Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells

The human brain is arguably the most complex structure among living organisms. However, the specific mechanisms leading to this complexity remain incompletely understood, primarily because of the poor experimental accessibility of the human embryonic brain. Over recent years, technologies based on pluripotent stem cells (PSCs) have been developed to generate neural cells of various ...

Defining the three cell lineages of the human blastocyst by single-cell RNA-seq

Here, we provide fundamental insights into early human development by single-cell RNA-sequencing of human and mouse preimplantation embryos. We elucidate conserved transcriptional programs along with those that are human specific. Importantly, we validate our RNA-sequencing findings at the protein level, which further reveals differences in human and mouse embryo gene expression. ...