DUSP6 (dual-specificity phosphatase 6), also known as MKP-3 [MAPK (mitogen-activated protein kinase) phosphatase-3] specifically inactivates ERK1/2 (extracellular-signal-regulated kinase 1/2) in vitro and in vivo. DUSP6/MKP-3 is inducible by FGF (fibroblast growth factor) signalling and acts as a negative regulator of ERK activity in key and discrete signalling centres that direct outgrowth and patterning in early vertebrate embryos. However, the molecular mechanism by which FGFs induce DUSP6/MKP-3 expression and hence help to set ERK1/2 signalling levels is unknown. In the present study, we demonstrate, using pharmacological inhibitors and analysis of the murine DUSP6/MKP-3 gene promoter, that the ERK pathway is critical for FGF-induced DUSP6/MKP-3 transcription. Furthermore, we show that this response is mediated by a conserved binding site for the Ets (E twenty-six) family of transcriptional regulators and that the Ets2 protein, a known target of ERK signalling, binds to the endogenous DUSP6/MKP-3 promoter. Finally, the murine DUSP6/MKP-3 promoter coupled to EGFP (enhanced green fluorescent protein) recapitulates the specific pattern of endogenous DUSP6/MKP-3 mRNA expression in the chicken neural plate, where its activity depends on FGFR (FGF receptor) and MAPK signalling and an intact Ets-binding site. These findings identify a conserved Ets-factor-dependent mechanism by which ERK signalling activates DUSP6/MKP-3 transcription to deliver ERK1/2-specific negative-feedback control of FGF signalling.

Innovative educational strategies can provide variety and enhance student learning while addressing complex logistical and financial issues facing modern anatomy education. Observe-Reflect-Draw-Edit-Repeat (ORDER), a novel cyclical artistic process, has been designed based on cognitivist and constructivist learning theories, and on processes of critical observation, reflection and drawing in anatomy learning. ORDER was initially investigated in the context of a compulsory first year surface anatomy practical (ORDER-SAP) at a United Kingdom medical school in which a cross-over trial with pre-post anatomy knowledge testing was utilized and student perceptions were identified. Despite positive perceptions of ORDER-SAP, medical student (n = 154) pre-post knowledge test scores were significantly greater (P < 0.001) with standard anatomy learning methods (3.26, SD = ±2.25) than with ORDER-SAP (2.17, ±2.30). Based on these findings, ORDER was modified and evaluated in the context of an optional self-directed gross anatomy online interactive tutorial (ORDER-IT) for participating first year medical students (n = 55). Student performance was significantly greater (P < 0.001) with ORDER-IT (2.71 ± 2.17) when compared to a control tutorial (1.31 ± 2.03). Performances of students with visual and artistic preferences when using ORDER were not significantly different (P > 0.05) to those students without these characteristics. These findings will be of value to anatomy instructors seeking to engage students from diverse learning backgrounds in a research-led, innovative, time and cost-effective learning method, in the context of contrasting learning environments. Anat Sci Educ 10: 7-22. © 2016 American Association of Anatomists.

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Cdx homeodomain transcription factors play important roles in the development of the vertebrate body axis and gut epithelium. Signaling involving FGF, wnt and retinoic acid ligands has been implicated in the regulation of individual Cdx genes. In this study we examine the requirement for FGF-dependent signal transduction pathways in the regulation of Cdx gene expression. In the amphibian Xenopus laevis the earliest expression of Cdx1, Cdx2 and Cdx4 is within the developing mesoderm. We show that a functional FGF signaling pathway is required for the normal expression of all three amphibian Cdx genes during gastrula stages. We show that FGF stimulation activates signaling through both the MAP kinase pathway and the PI-3 kinase pathway in Xenopus tissue explants. However, our analysis of these pathways in gastrula stage embryos indicates that the MAP kinase pathway is required for Cdx gene expression, whereas the PI-3 kinase pathway is not. We show that FGF and wnt signaling can interact in the regulation of Cdx genes and during gastrula stages the normal expression of the Cdx genes requires the activity of both pathways. Furthermore, we show that wnt mediated Cdx regulation is independent of the MAP kinase pathway.