The dispatched (disp) gene is required for long-range Hedgehog (Hh) signaling in Drosophila. Here, we demonstrate that one of two murine homologs, mDispA, can rescue disp function in Drosophila and is essential for all Hh patterning activities examined in the early mouse embryo. Embryonic fibroblasts lacking mDispA respond normally to exogenously provided Sonic hedgehog (Shh) signal, but are impaired in stimulation of other responding cells when expressing Shh. We have developed a biochemical assay that directly measures the activity of Disp proteins in release of soluble Hh proteins. This activity is disrupted by alteration of residues functionally conserved in Patched and in a related family of bacterial transmembrane transporters, thus suggesting similar mechanisms of action for all of these proteins.
The current food supply in many parts of the world differs substantially from that which existed during most of human evolution. It is characterized by a high variety of palatable foods with high energy density and low fiber content. Many foods can be eaten very quickly, and there is not always congruency between the sensory properties of the food and the subsequent metabolic consequences of its ingestion, (e.g., as in the consumption of artificially sweetened foods). It is not presently known how the human body copes with this incongruent food environment in terms of short-term satiety responses and long(er)-term regulation of food intake. Cephalic phase responses (CPRs) are innate and learned physiological responses to sensory signals that prepare the gastrointestinal tract for the optimal processing of ingested foods. CPRs could be affected by inconsistencies in the associations between sensory signals and subsequent post-ingestive consequences. Reviewed here are the available data on how CPRs affect the control of food intake.
Summary The aim of this paper is to describe and discuss relevant aspects of the assessment of physiological functions – and related biomarkers – implicated in the regulation of appetite in humans. A short introduction provides the background and the present state of biomarker research as related to satiety and appetite. The main focus of the paper is on the gastrointestinal tract and its functions and biomarkers related to appetite for which sufficient data are available in human studies. The first section describes how gastric emptying, stomach distension and gut motility influence appetite; the second part describes how selected gastrointestinal peptides are involved in the control of satiety and appetite (ghrelin, cholecystokinin, glucagon‐like peptide, peptide tyrosin‐tyrosin) and can be used as potential biomarkers. For both sections, methodological aspects (adequacy, accuracy and limitation of the methods) are described. The last section focuses on new developments in techniques and methods for the assessment of physiological targets involved in appetite regulation (including brain imaging, interesting new experimental approaches, targets and markers). The conclusion estimates the relevance of selected biomarkers as representative markers of appetite regulation, in view of the current state of the art.
Teashirt binds to, and requires, Armadillo for the naked cell-fate choice in the larval trunk. Teashirt is required for trunk segment identity, suggesting that Teashirt provides a region-specific output to Armadillo activity. Further modulation of Wingless is achieved in homologous parts of each trunk segment where Wingless and Teashirt are especially active. Our results provide a novel, cell-intrinsic mechanism to explain the modulation of the activity of the Wingless signalling pathway.
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