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SRP056748
Danio rerio
4 Downloadable Samples
IlluminaHiSeq2000
Description
Transcriptional events during initial vertebrate heart development in vivo remain poorly understood. Mesp1, a bHLH transcription factor, has been described as the earliest transcriptional regulator of cardiac progenitors in multiple species, and represents an excellent candidate for the investigation of relevant targets during cardiovascular development. We report here that both depletion and mutation of Mespaa, the zebrafish homolog of mammalian Mesp1, lead to randomization of cardiac looping, together with significant cardiac morphogenesis defects. These disruptions are preceded by a defect in cardiac left-right asymmetry. Surprisingly, the defect in asymmetry was found to occur independently of defects in the transient organ of laterality, the Kupffer’s vesicle (KV). We show that Mespaa regulates miR-430 expression during gastrulation to control the levels of Nodal signaling, and that this regulation is required for asymmetric laterality signaling in the prospective heart field. Ectopic expression of miR-430 is sufficient to induce cardiac laterality defects, and consistent with Mespaa over-expression in this system, the reduction of miR-430 leads to cardia bifida. This study reveals a novel transcriptional regulation of miR-430 by Mespaa and a role for this pathway in cardiac laterality during gastrulation.
Publication Title
No associated publication
Alternate Accession IDs
None
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
We assessed the impact of glucose transporter Glut2 gene inactivation in adult mouse liver (LG2KO mice). This suppressed hepatic glucose uptake but not glucose output. In the fasted state, expression of carbohydrate responsive element-binding protein (ChREBP) and its glycolytic and lipogenic target genes was abnormally elevated. Feeding, energy expenditure, and insulin sensitivity were identical in LG2KO and control mice. Glucose tolerance was normal early after Glut2 inactivation but intolerance developed at later time. This was caused by progressive impairment of glucose-stimulated insulin secretion even though beta-cell mass and insulin content remained normal. Liver transcript profiling revealed a coordinate down-regulation of cholesterol biosynthesis genes in LG2KO mice. This was associated with reduced hepatic cholesterol in fasted mice and a 30 percent reduction in bile acid production. We showed that chronic bile acids or FXR agonist treatment of primary islets increases glucose-stimulated insulin secretion, an effect not seen in islets from fxr-/- mice. Collectively, our data show that glucose sensing by the liver controls beta-cell glucose competence, through a mechanism that likely depends on bile acid production and action on beta-cells.
Publication Title
Hepatic glucose sensing is required to preserve β cell glucose competence.
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Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Barrier integrity is central to the maintenance of a healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic diseases such as food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD, we report that a fermentable fibre-rich diet alleviates AD severity and systemic allergen sensitization. The gut-skin axis underpins this phenomenon through SCFA, which strengthen skin barrier integrity by altering mitochondrial metabolism of epidermal keratinocytes. SCFA promote keratinocyte differentiation and the production of key structural lipids, resulting in enhanced barrier function. Our results demonstrate that dietary fibre and SCFA mitigate AD by improving barrier integrity, ultimately limiting early systemic allergen sensitization and development of disease. Overall design: 16 Samples, 4 groups in duplicate
Publication Title
Gut-derived short-chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation.
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Sample Metadata Fields
Genotype, Disease, Disease stage, Treatment, Subject
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