Department of Molecular and Cell Biology
University of California, Berkeley
BMP signaling in stem cell development in the gut.
The radial axis of the gut, from crypt to villus, has long provided an attractive paradigm for understanding how signaling pathways converge on the proliferation of stem cells in the crypt, and the subsequent differentiation of cells as they move towards the villus and are ultimately shed from the tip of the villus into the gut lumen. The establishment of this crypt to villus axis is much less well understood, and we have gained insights from the study of conditional mutants of the Noggin gene. Postnatal loss of Noggin leads to the failure of cells lining the gut to proliferate, concomitant with a failure to differentiate. The gut wall then becomes disorganized and ultimately disintegrates. Current work is focused on the role of Noggin, which is expressed in a layer just below the prospective crypts, in the maintenance of Wnt signaling, proliferation and differentiation.