ABSTRACT
The importance of the Wnt-signaling pathway on the regulation and maintenance of the intestinal stem cell (ISC) population is well recognized. However, our current knowledge base is founded on models using systems of gross deregulation of the Wnt-signaling pathway. Given the importance of this signaling pathway on intestinal homeostasis, there is a need to explore the role of more subtle alterations in Wnt-signaling levels within this tissue. Herein, we have used a model of Apc2 loss to meet this aim. Apc2 is a homolog of Apc which can also form a destruction complex capable of binding ß-catenin, albeit less efficiently than Apc. We show that systemic loss of Apc2 results in an increase in the number of cells displaying nuclear ß-catenin at the base of the intestinal crypt. This subsequently impacts the expression levels of several ISC markers and the fitness of ISCs as assessed by organoid formation efficiency. This work provides the first evidence that the function and fitness of ISCs can be altered by even minor misregulation of the Wnt-signaling pathway. Our data highlights the importance of correct maintenance of this crucial signaling pathway in the maintenance and function of the ISC population. Stem Cells 2018;36:114-122.
Subject(s)
Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome/metabolism , Intestinal Mucosa/metabolism , Intestines/cytology , Stem Cells/cytology , Stem Cells/metabolism , Wnt Signaling Pathway , Animals , Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome/deficiency , Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome/genetics , Apoptosis/physiology , Intestine, Small/cytology , Intestine, Small/metabolism , Mice , Mice, Knockout , Models, AnimalABSTRACT
The present study examined the moderating role of attitudinal ambivalence within the theory of planned behaviour (TPB). Attitude, subjective norm, perceived behavioural control (PBC), behavioural intentions and self-reported behaviour were assessed in relation to 20 healthy eating behaviours in a prospective questionnaire design in 232 members of the general public in the UK. Between-participants univariate and multivariate analyses indicated attitude-behaviour and PBC-behaviour relationships to be weaker in higher ambivalence compared to lower ambivalence respondents. These effects were confirmed in within-participants analyses. The findings are discussed in terms of the role of ambivalence in furthering our understanding of relationships in the TPB.
