? Inherited or acquired abnormalities of the gastrointestinal tract represent a large share of chronic disease in infants and children, often requiring costly long-term medical support or organ transplantation. Because these diseases constitute a costly healthcare burden, the study of Gl development is of high priority. Developmental biology of the digestive system aims to further the understanding of both congenital and acquired forms of pediatric gastrointestinal disease with the goal to ultimately advance therapies for Gl diseases. The vertebrate body is generated from three germ layers: ectoderm, endoderm and mesoderm. The development of these three germ layers and the early reciprocal interactions between them are accepted to be conserved between species. The epithelium of the vertebrate gastrointestinal tract is derived from the endoderm and the muscular layers and mesenchyme are derived from the visceral mesoderm. It is understood that the endoderm and mesoderm need intrinsic and extrinsic factors for coordinated development of the Gl tract. This process, known as epithelial-mesenchymal interaction, is indispensable both for the development of the Gl tract and for its integrity into adulthood. The epithelium has been the focus of most studies to date because of the clinical implications of epithelial biology in the understanding and treatment of cancer. Recently the importance of signaling from the mesoderm/mesenchyme in tissue homeostasis and repair has been highlighted because of the implications for epithelial and stem-cell biology. Likewise, there is a conspicuous gap in the current knowledge of Gl development. It is less well understood how the mesoderm surrounding the gut develops and contributes to the development of the adjacent endoderm. Preliminary evidence suggests that Wnt signaling plays a major role in the patterning and maintenance of the visceral mesoderm and in its interactions with the adjacent endoderm. A potential mediator and of Wnt signaling appears to be FoxF1, the key transcription factor for the development and maintenance of the visceral mesoderm, previously known to be regulated by BMP4. Thus, it is the overall aim of this proposal to examine the role of Wnt signaling in development of the visceral mesoderm, its influence on endoderm development, and the role of FoxF1 and BMP4 in these processes. ? ?
| McLin, Valerie A; Henning, Susan J; Jamrich, Milan (2009) The role of the visceral mesoderm in the development of the gastrointestinal tract. Gastroenterology 136:2074-91 |
