Coordination of Cell Differentiation and Migration in Mathematical Models of Caudal Embryonic Axis Extension

Vertebrate embryos display a predominant head-to-tail body axis whose formation is associated with the progressive development of post-cranial structures from a pool of caudal undifferentiated cells. This involves the maintenance of active FGF signaling in this caudal region as a consequence of the restricted production of the secreted factor FGF8. FGF8 is transcribed specifically in the caudal precursor region and is down-regulated as cells differentiate and the embryo extends caudally. We are interested in understanding the progressive down-regulation of FGF8 and its coordination with the caudal movement of cells which is also known to be FGF-signaling dependent. Our study is performed using mathematical modeling and computer simulations. We use an individual-based hybrid model as well as a caricature continuous model for the simulation of experimental observations (ours and those known from the literature) in order to examine possible mechanisms that drive differentiation and cell movement during the axis elongation. Using these models we have identified a possible gene regulatory network involving self-repression of a caudal morphogen coupled to directional domain movement that may account for progressive down-regulation of FGF8 and conservation of the FGF8 domain of expression. Furthermore, we have shown that chemotaxis driven by molecules, such as FGF8 secreted in the stem zone, could underlie the migration of the caudal precursor zone and, therefore, embryonic axis extension. These mechanisms may also be at play in other developmental processes displaying a similar mode of axis extension coupled to cell differentiation

Maternal Wnt/β-Catenin Signaling Coactivates Transcription through NF-κB Binding Sites during Xenopus Axis Formation

Maternal Wnt/β-Catenin signaling establishes a program of dorsal-specific gene expression required for axial patterning in Xenopus. We previously reported that a subset of dorsally expressed genes depends not only on Wnt/β-Catenin stimulation, but also on a MyD88-dependent Toll-like receptor/IL1-receptor (TLR/IL1-R) signaling pathway. Here we show that these two signal transduction cascades converge in the nucleus to coactivate gene transcription in blastulae through a direct interaction between β-Catenin and NF-κB proteins. A transdominant inhibitor of NF-κB, ΔNIκBα, phenocopies loss of MyD88 protein function, implicating Rel/NF-κB proteins as selective activators of dorsal-specific gene expression. Sensitive axis formation assays in the embryo demonstrate that dorsalization by Wnt/β-Catenin requires NF-κB protein activity, and vice versa. Xenopus nodal-related 3 (Xnr3) is one of the genes with dual β-Catenin/NF-κB input, and a proximal NF-κB consensus site contributes to the regional activity of its promoter. We demonstrate in vitro binding of Xenopus β-Catenin to several XRel proteins. This interaction is observed in vivo upon Wnt-stimulation. Finally, we show that a synthetic luciferase reporter gene responds to both endogenous and exogenous β-Catenin levels in an NF-κB motif dependent manner. These results suggest that β-Catenin acts as a transcriptional co-activator of NF-κB-dependent transcription in frog primary embryonic cells

Exploring the power of high-level postgraduate international partnership work based learning programmes

This chapter explores students’ reflections of their experiential learning whilst enrolled on an HE work based learning (WBL) international internship programme jointly developed by the University of Chester and the Mountbatten Institute. The chapter commences with some background to help set in context why these two organisations came together to form this unique inter-organisational partnership involving the partner delivering and assessing, and the HEI accrediting the programme. Then using data gained from student evaluations together with quotes obtained from students’ reflective learning logs, submitted as part of their final project at the end of the taught element of the programme, the chapter explores students’ perceptions of what they perceive they have gained from this experience which they can take forward into their future careers. As such it provides a unique insight into the nature and value of this international learning experience