Investigating the Development of the Digestive Tract
Intestinal malrotation occurs in as many as 1 in 500 human births (0.2% of the population) and poses significant risk for life-threatening complications in babies and children. No clear inheritance pattern has been identified for intestinal malrotation, suggesting a multifactorial etiology involving genetic, epigenetic and/or environmental causes.
Normal digestive anatomy is a consequence of the dramatic elongation, left-right asymmetric looping and rotation of the primitive gut tube during fetal development, but the cellular and molecular mechanisms underlying these events in gut morphogenesis are poorly understood.
Our lab employs chemical genetic strategies in amphibian embryos to investigate the mechanisms of digestive tract morphogenesis, understand the etiology of intestinal malrotation, and define the effects of chemicals and toxins on gut development.
Amphibian embryos, such as those of the frog, Xenopus laevis (left), have provided important insights into the mechanisms of animal development and morphogenesis, and are now an emerging model for chemical genetic studies.
Drug-like small molecules can be used to modulate protein activity in developing aquatic embryos. Similar to classic genetic screens, this "chemical genetic" approach is revealing the molecular mechanisms of gastrointestinal tract development.
The anatomy and physiology of the digestive tract determine how well an organism can assimilate energy from its environment...which directly impacts its potential habitat and fitness. Our small molecule screens are revealing the molecular developmental changes that accompany the evolution of novel digestive organ traits in non-model amphibian species.