Expression of Notch pathway components in fetal and adult mouse small intestine.

Cell-to-cell communication mediated by the evolutionary conserved Notch signalling pathway regulates cell fate decisions and patterning in various tissues in invertebrates and vertebrates (Science 284 (1999) 770). In mouse, four Notch receptors, five ligands of the delta and Serrate types, three fringe glycosyltransferases that modify Notch, and a growing number of direct transcriptional targets of Notch are known. Mutational analysis of Hes1 (Nat. Genet. 24 (2000) 36) and Math1 (Science 294 (2001) 2155) have implicated Notch signalling in the regulation of intestinal epithelium development and homeostasis. Here, we describe the expression of the genes encoding the murine Notch receptors (Notch1-4), the ligands (delta1, 3, 4 and Jagged1, 2), the modifying glycosyltransferases of the fringe family (Lfng, Mfng, Rfng) and four Hes genes (Hes1, 5, 6, 7) in the mouse small intestine during fetal (E13.5 and E18.5) and postnatal (P25) development. All analyzed Notch pathway components were expressed in the intestine, although at different levels and with varying spatial and temporal distribution, consistent with roles of Notch signalling at various stages of intestinal development and renewal.

Identification of mouse genes with highly specific expression patterns in differentiated intestinal epithelium.

BACKGROUND & AIMS: Few genes that regulate intestinal epithelium development, homeostasis, or function are known. We reasoned that potential candidate regulators of these processes could be identified based on their activation during intestinal epithelium development and their subsequent specific and restricted expression. METHODS: Genes were identified by differential display and microarray analyses, further selected according to sequence and UniGene expression profiles, and analyzed by RNA in situ hybridization of mouse fetal and adult intestines and in intestinal polyp tissue. RESULTS: Five genes with unknown physiological function predominantly or exclusively expressed in the intestinal epithelium were identified. Their expression is activated at distinct times during intestinal development and maturation and is maintained in highly specific, spatially distinct patterns in the adult intestinal epithelium. Two of the genes were up-regulated in intestinal tumors, 1 was down-regulated, and 2 were apparently unaltered. CONCLUSIONS: Based on sequence and expression, the identified genes represent good candidates for regulators of intestinal epithelium integrity or function. Their expression patterns suggest a morphologically not obvious molecular regionalization of the intestinal epithelium along the crypt villus axis. This approach should be an efficient means to identify novel genes required for intestinal epithelium homeostasis and function.