http://repub.eur.nl/res/aut/29687/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/37414/ 2012-10-17T00:00:00Z Histology of the mature gastro-intestinal tract: The gastro-intestinal tract is organized in four distinct layers, which are consistent from mouth to anus. Surrounding the gastro-intestinal lumen is the mucosa, followed by the submucosa, tunica muscularis and serosa. The inner layer of any epithelial-lined hollow organ (e.g., mouth, gut, trachea, lung, etc) is called the mucosa, which itself consists of the epithelium, lamina propria and the muscularis mucosa, which forms the boundary between mucosa and submucosa. The submucosa is a connective tissue layer supporting the mucosa and allows flexibility during peristalsis. It contains a vascular plexus, which gives rise to the capillary bed of the mucosa and also a delicate nerve network, called Meissner’s plexus. The tunica muscularis consists of an inner circular layer and an outer longitudinal layer. Between the two muscle layers lies the Auerbach’s plexus. Coordinated contraction of these layers is responsible for rhythmic peristalsis. The adventitia or the serosa is the outermost layer of the gastrointestinal tract and has a supportive function. http://repub.eur.nl/res/pub/37979/ 2012-09-01T00:00:00Z Wnt5a is essential during embryonic development, as indicated by mouse . Wnt5a knockout embryos displaying outgrowth defects of multiple structures including the gut. The dynamics of Wnt5a involvement in these processes is unclear, and perinatal lethality of . Wnt5a knockout embryos has hampered investigation of Wnt5a during postnatal stages in vivo. Although in vitro studies have suggested a relevant role for Wnt5a postnatally, solid evidence for a significant impact of Wnt5a within the complexity of an adult organism is lacking. We generated a tightly-regulated inducible . Wnt5a transgenic mouse model and investigated the effects of Wnt5a induction during different time-frames of embryonic development and in adult mice, focusing on the gastrointestinal tract. When induced in embryos from 10.5. dpc onwards, Wnt5a expression led to severe outgrowth defects affecting the gastrointestinal tracts, limbs, facial structures and tails, closely resembling the defects observed in . Wnt5a knockout mice. However, Wnt5a induction from 13.5. dpc onwards did not cause this phenotype, indicating that the most critical period for Wnt5a in embryonic development is prior to 13.5. dpc. In adult mice, induced Wnt5a expression did not reveal abnormalities, providing the first in vivo evidence that Wnt5a has no major impact on mouse intestinal homeostasis postnatally. Protein expression of Wnt5a receptor Ror2 was strongly reduced in adult intestine compared to embryonic stages. Moreover, we uncovered a regulatory process where induction of Wnt5a causes downregulation of its receptor Ror2. Taken together, our results indicate a role for Wnt5a during a restricted time-frame of embryonic development, but suggest no impact during homeostatic postnatal stages. http://repub.eur.nl/res/pub/24083/ 2009-07-01T00:00:00Z To develop a sensitive and inducible system to study intestinal biology, we generated a transgenic mouse model expressing the reverse tetracycline transactivator rtTA2-M2 under control of the 12.4 kb murine Villin promoter. The newly generated Villin-rtTA2-M2 mice were then bred with the previously developed tetOHIST1H2BJ/GFP model to assess inducibility and tissues-pecificity. Expression of the histone H2B-GFP fusion protein was observed exclusively upon doxycycline induction and was uniformly distributed throughout the intestinal epithelium. The Villin-rtTA2-M2 was also found to drive transgene expression in the developing mouse intestine. Furthermore, we could detect transgene expression in the proximal tubules of the kidney and in a population of alleged gastric progenitor cells. By administering different concentrations of doxycycline, we show that the Villin-rtTA2-M2 system drives transgene expression in a dosage-dependent fashion. Thus, we have generated a novel doxycycline-inducible mouse model, providing a valuable tool to study the effect of different gene dosages on intestinal physiology and pathology.