The Sight Loss and Vision Priority Setting Partnership (SLV-PSP): overview and results of the research prioritisation survey process

Objectives: The Sight Loss and Vision Priority Setting Partnership aimed to identify research priorities relating to sight loss and vision through consultation with patients, carers and clinicians. These priorities can be used to inform funding bodies’ decisions and enhance the case for additional research funding. Design: Prospective survey with support from the James Lind Alliance. Setting: UK-wide National Health Service (NHS) and non-NHS. Participants: Patients, carers and eye health professionals. Academic researchers were excluded solely from the prioritisation process. The survey was disseminated by patient groups, professional bodies, at conferences and through the media, and was available for completion online, by phone, by post and by alternative formats (Braille and audio). Outcome measure: People were asked to submit the questions about prevention, diagnosis and treatment of sight loss and eye conditions that they most wanted to see answered by research. Returned survey questions were reviewed by a data assessment group. Priorities were established across eye disease categories at final workshops. Results: 2220 people responded generating 4461 submissions. Sixty-five per cent of respondents had sight loss and/or an eye condition. Following initial data analysis, 686 submissions remained which were circulated for interim prioritisation (excluding cataract and ocular cancer questions) to 446 patients/carers and 218 professionals. The remaining 346 questions were discussed at final prioritisation workshops to reach agreement of top questions per category. Conclusions: The exercise engaged a diverse community of stakeholders generating a wide range of conditions and research questions. Top priority questions were established across 12 eye disease categories. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial

An NF-κB and Slug Regulatory Loop Active in Early Vertebrate Mesoderm

BACKGROUND: In both Drosophila and the mouse, the zinc finger transcription factor Snail is required for mesoderm formation; its vertebrate paralog Slug (Snai2) appears to be required for neural crest formation in the chick and the clawed frog Xenopus laevis. Both Slug and Snail act to induce epithelial to mesenchymal transition (EMT) and to suppress apoptosis. METHODOLOGY & PRINCIPLE FINDINGS: Morpholino-based loss of function studies indicate that Slug is required for the normal expression of both mesodermal and neural crest markers in X. laevis. Both phenotypes are rescued by injection of RNA encoding the anti-apoptotic protein Bcl-xL; Bcl-xL's effects are dependent upon IκB kinase-mediated activation of the bipartite transcription factor NF-κB. NF-κB, in turn, directly up-regulates levels of Slug and Snail RNAs. Slug indirectly up-regulates levels of RNAs encoding the NF-κB subunit proteins RelA, Rel2, and Rel3, and directly down-regulates levels of the pro-apopotic Caspase-9 RNA. CONCLUSIONS/SIGNIFICANCE: These studies reveal a Slug/Snail–NF-κB regulatory circuit, analogous to that present in the early Drosophila embryo, active during mesodermal formation in Xenopus. This is a regulatory interaction of significance both in development and in the course of inflammatory and metastatic disease

Current perspectives of the signaling pathways directing neural crest induction

The neural crest is a migratory population of embryonic cells with a tremendous potential to differentiate and contribute to nearly every organ system in the adult body. Over the past two decades, an incredible amount of research has given us a reasonable understanding of how these cells are generated. Neural crest induction involves the combinatorial input of multiple signaling pathways and transcription factors, and is thought to occur in two phases from gastrulation to neurulation. In the first phase, FGF and Wnt signaling induce NC progenitors at the border of the neural plate, activating the expression of members of the Msx, Pax, and Zic families, among others. In the second phase, BMP, Wnt, and Notch signaling maintain these progenitors and bring about the expression of definitive NC markers including Snail2, FoxD3, and Sox9/10. In recent years, additional signaling molecules and modulators of these pathways have been uncovered, creating an increasingly complex regulatory network. In this work, we provide a comprehensive review of the major signaling pathways that participate in neural crest induction, with a focus on recent developments and current perspectives. We provide a simplified model of early neural crest development and stress similarities and differences between four major model organisms: Xenopus, chick, zebrafish, and mouse