pRb-mediated control of epithelial cell proliferation and Indian hedgehog expression in mouse intestinal development.
BACKGROUND
Self-renewal of the epithelium of the small intestine is a highly regulated process involving cell proliferation and differentiation of stem cells or progenitor cells located at the bottom of the crypt, ending ultimately with extrusion of the terminally differentiated cells at the tip of villus.


RESULTS
Here, we utilized the Cre/loxP system to investigate the function of the retinoblastoma protein, pRb in intestinal epithelium. pRb null mice displayed a profoundly altered development of the intestine with increased proliferation and abnormal expression of differentiation markers. Loss of pRb induces cell hyperproliferation in the proliferative region (crypt) as well as in the differentiated zone (villi). The absence of pRb further results in an increase in the population of enterocytes, goblet, enteroendocrine and Paneth cells. In addition, differentiated enteroendocrine cells failed to exit the cell cycle in the absence of pRb. These proliferative changes were accompanied by increased expression of Indian hedgehog and activation of hedgehog signals, a known pathway for intestinal epithelial cell proliferation.


CONCLUSIONS
Our studies have revealed a unique function of pRb in intestine development which is critical for controlling not only the proliferation of a stem cell or progenitor cell population but that of terminally differentiated cells as well.
Yang
Hai-Su
HS
Molecular Oncology Research Institute, Tufts-New England Medical Center, 75 Kneeland Street, Boston, MA 02111, USA. hyang@tufts-nemc.org
Hinds
Philip W
PW
D000818:Animals; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology*; D007422:Intestines / Q000254:growth & development*; D051379:Mice; D008822:Mice, Transgenic; D016160:Retinoblastoma Protein / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D053823:Hedgehog Proteins; D016160:Retinoblastoma Protein; C514061:ihh protein, mouse