Coordination between functionally related adjacent tissues is essential during development. For example, formation of trunk neural crest cells (NCCs) is highly influenced by the adjacent mesoderm, but the molecular mechanism involved is not well understood. As part of this mechanism, fibroblast growth factor (FGF) and retinoic acid (RA) mesodermal gradients control the onset of neurogenesis in the extending neural tube. In this paper, using gain-and loss-of-function experiments, we show that caudal FGF signaling prevents premature specification of NCCs and, consequently, premature epithelial-mesenchymal transition (EMT) to allow cell emigration. In contrast, rostrally generated RA promotes EMT of NCCs at somitic levels. Furthermore, we show that FGF and RA signaling control EMT in part through the modulation of elements of the bone morphogenetic protein and Wnt signaling pathways. These data establish a clear role for opposition of FGF and RA signaling in control of the timing of NCC EMT and emigration and, consequently, co-ordination of the development of the central and peripheral nervous system during vertebrate trunk elongation.

Genes of the SOX family of high‐mobility group transcription factors are essential during nervous system development. In this study, we show that SOX5 is expressed by neural progenitors in the chick spinal cord and is turned off as differentiation proceeds. The overexpression of SOX5 in neural progenitors causes premature cell cycle exit and prevents terminal differentiation. Conversely, knocking down SOX5 protein extends the proliferative period of neural progenitors and causes marked cell death in a dorsal interneuron (dI3) population. Furthermore, SOX5 reduces WNT–β‐catenin signalling, thereby triggering the expression of the negative regulator of the pathway axin2. We propose that SOX5 regulates the timing of cell cycle exit by opposing WNT–β‐catenin activity on cell cycle progression.

Progress in understanding neurodegenerative cell biology in Parkinson's disease (PD) has been hampered by a lack of predictive and relevant cellular models. In addition, the lack of an adequatein vitrohuman neuron cell-based model has been an obstacle for the uncover of new drugs for treating PD. The ability to generate induced pluripotent stem cells (iPSCs) from PD patients and a refined capacity to differentiate these iPSCs into DA neurons, the relevant disease cell type, promises a new paradigm in drug development that positions human disease pathophysiology at the core of preclinical drug discovery. Disease models derived from iPSC that manifest cellular disease phenotypes have been established for several monogenic diseases, but iPSC can likewise be used for phenotype-based drug screens in complex diseases for which the underlying genetic mechanism is unknown. Here, we highlight recent advances as well as limitations in the use of iPSC technology for modelling PD “in a dish” and for testing compounds against human disease phenotypesin vitro. We discuss how iPSCs are being exploited to illuminate disease pathophysiology, identify novel drug targets, and enhance the probability of clinical success of new drugs.

Introduction: LAG-3 is checkpoint inhibitor in cancer that coordinates the downregulation of the proliferation of antigen-specific lymphocytes. There is a great need to discover and develop new therapies focused on inhibiting the action of LAG-3 and consequently improving the immune response in the various types of cancer. Areas covered: The patent literature reveals novel therapies, which provide information on cancer therapies. The authors used the patent databases of the six main patent offices of the world: United States Patent and Trademark Office, European Patent Office, World Intellectual Property Organization, Japan Patent Office, State Intellectual Property Office of China and Korean Intellectual Property Office, to generate a detailed landscape of patents and patent applications of active companies related to LAG-3 inhibitors. Specific patents have been grouped into innovative patents and adopting patents. Expert opinion: There is a continuing development of LAG-3 inhibitors, and these inhibitors are being used in combination with other cancer treatment schemes, for example, antibodies against PD-1, PD-L1, and CTLA-4. Immutep and IO Therapeutics were the leaders in generating innovator patents, followed by Gustave Roussy Institute, and Applied Research Systems ARS. Dana-Farber Cancer Institute was the leader in the generation of adopter patents, followed by Novartis .

Aberrant glycosylation is a characteristic of tumour cells. The expression of certain glycan structures has been associated with poor prognosis. In cervical carcinoma, changes in the expression levels of some glycogenes have been associated with lymph invasion. Human papillomavirus (HPV) infection is one of the most important factors underlying the development of cervical cancer. The HPV oncoproteins E6 and E7 have been implicated in cervical carcinogenesis and can modify the host gene expression profile. The roles of these oncoproteins in glycosylation changes have not been previously reported. To determine the effect of the E6 and E7 oncoproteins on glycogene expression we partially silenced the E6 and E7 oncogenes in HeLa cells, we performed a microarray expression assay to identify altered glycogenes and quantified the mRNA levels of glycogenes by RT-qPCR. A protein-protein interaction network was constructed to identify potentially altered glycosylation pathways. The microarray analysis showed 9 glycogenes that were upregulated and 7 glycogenes that were downregulated in HeLa shE6/E7 cells. Some of these genes participate in glycosylation related to Notch proteins and O-glycans antigens. Our results support that E6 and E7 oncoproteins could modify glycogene expression the products of which participate in the synthesis of structures implicated in proliferation, adhesion and apoptosis.