👤 Sarah Childs

The Musashi family of mRNA translational regulators controls both physiological and pathological stem cell self-renewal primarily by repressing target mRNAs that promote differentiation. In response to differentiation cues, Musashi can switch from a repressor to an activator of target mRNA translation. However, the molecular events that distinguish Musashi-mediated translational activation from repression are not understood. We have previously reported that Musashi function is required for the maturation of Show less

The mechanisms responsible for changes to long-chain polyunsaturated fatty acid (LC PUFA) status during pregnancy have not been fully elucidated. Tissue samples were collected from virgin and pregnant (day 12 and 20) female rats. LC PUFA status, sex hormone concentrations and hepatic mRNA expression of FADS1, FADS2 and elongase were assessed. Day 20 gestation females had higher plasma and liver docosahexaenoic acid and lower arachidonic acid content than virgin females (P<0.05). There was higher FADS2 mRNA expression during pregnancy (P=0.051). Progesterone and oestradiol concentrations positively correlated with hepatic FADS2 mRNA expression (P=0.043, P=0.004). Progesterone concentration positively correlated with hepatic n-6 docosapentaenoic acid content (P=0.006), and inversely correlated with intermediates in LC PUFA synthesis including n-3 docosapentaenoic acid, γ-linolenic acid and 20:2n-6 (P<0.05). Changes in progesterone and oestradiol during pregnancy may promote the synthesis of LC PUFA via increased FADS2 expression. Show less

Growing evidence suggests that a genetic program specifies the identity of arteries and veins before the onset of circulation. A signaling cascade involving sonic hedgehog (Shh), vascular endothelial growth factor (VEGF), the VEGF receptor 2 (VEGFR2), homeobox proteins Foxc1 and Foxc2, the Notch receptor, and the downstream transcription factor gridlock is required for expression of arterial markers, whereas only a single transcription factor, COUP-TFII (chicken ovalbumin upstream promoter-transcription factor II), has previously been implicated in maintaining venous fate. Recent work has now implicated two competing pathways downstream of VEGFR2 in arterial versus venous specification: Activation of the phospholipase C-gamma (PLC-gamma)-mitogen-activated protein kinase (MAPK) pathway acts in arterial specification, whereas the phosphoinositide 3-kinase (PI3K)-Akt pathway acts to allow a venous fate by inhibition of the PLC-gamma-MAPK pathway. Here, we review this work and discuss how activation of the MAPK signaling cascade could stimulate an arterial fate. Show less

Arteries and veins are morphologically, functionally and molecularly very different, but how this distinction is established during vasculogenesis is unknown. Here we show, by lineage tracking in zebrafish embryos, that angioblast precursors for the trunk artery and vein are spatially mixed in the lateral posterior mesoderm. Progeny of each angioblast, however, are restricted to one of the vessels. This arterial-venous decision is guided by gridlock (grl), an artery-restricted gene that is expressed in the lateral posterior mesoderm. Graded reduction of grl expression, by mutation or morpholino antisense, progressively ablates regions of the artery, and expands contiguous regions of the vein, preceded by an increase in expression of the venous marker EphB4 receptor (ephb4) and diminution of expression of the arterial marker ephrin-B2 (efnb2). grl is downstream of notch, and interference with notch signalling, by blocking Su(H), similarly reduces the artery and increases the vein. Thus, a notch-grl pathway controls assembly of the first embryonic artery, apparently by adjudicating an arterial versus venous cell fate decision. Show less