Year: 2004
Type: article
Abstract: Introduction: Molecular control of growth and morphogenesis during intestinal development is poorly understood. Previously, the NIL PER OS (NPO) gene was found to be essential to the endoderm-intestine transition in zebrafish (1)). Loss of NPO function leads to a hypoplastic, poorly developed intestine, and its overexpression causes hyperproliferation of intestinal epithelium. These data suggest the hypothesis that NPO acts to specify intestinal epithelial progenitors cells. The aim of this study is to determine the pattern of NPO expression in developing, adult, and neoplastic intestine. Since the progenitor cell compartment of the intestine is spatially distinct, expression of NPO in this compartment, and promiscuous expression in tumors would be consistent with our hypothesis. Methods: We used staged mouse embryos and discarded human surgical specimens of colon cancer, polyp and adult normal tissue to study NPO expression by in situ hybridization. Cultured colon cancer cells (caco-2) were subjected to RT-PCR analysis to determine NPO expression levels as a function of their differentiation state. Results: We found that expression of NPO during mouse development is dynamic, similar to that in zebrafish. As the villi form, diffuse NPO expression in the unpatterned endoderm becomes progressively restricted to a subset of intestinal epithelial cells that are located in the the intervillous regions, and then in the crypts of Lieberkuhn of the adult. We also examined NPO expression in human colon carcinoma, which exhibits many features of crypt cells. Indeed, NPO was expressed at a much higher level in neoplastic compared to normal tissue. Using the caco-2 cell model, we found that the NPO expression level declined markedly upon confluence-induced differentiation. Conclusion: Our data suggest that NPO may play a role in specifying epithelial progenitor cells in several different contexts: during development, homeostasis and neoplasia. Further study will be needed to determine if NPO is functionally required for each of these processes. The npo protein binds RNA and is thought to be involved in ribosomal biogenesis (2), 3)). Thus regulation of ribosomal biogenesis by NPO may play a role in progenitor cell specification.
Authors: A. N. Mayer, R. E. Palmer, D. A. Haber
Institutions: Medical College of Wisconsin, Massachusetts General Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4390567656