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First published online 2 February 2005
doi: 10.1242/dev.01644
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1 Vertebrate Development Laboratory, Cancer Research UK London Research
Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
2 Division of Biomedical Sciences, Imperial College London, Exhibition Road,
London SW7 2AZ, UK
3 Electron Microscopy Unit, Cancer Research UK London Research Institute, 44
Lincoln's Inn Fields, London WC2A 3PX, UK
4 Department of Comparative Genomics, GlaxoSmithKline, Harlow CM19 5AW, UK
* Author for correspondence (e-mail: julian.lewis{at}cancer.org.uk)
Accepted 15 December 2004
The transparency of the juvenile zebrafish and its genetic advantages make it an attractive model for study of cell turnover in the gut. BrdU labelling shows that the gut epithelium is renewed in essentially the same way as in mammals: the villi are lined with non-dividing differentiated cells, while cell division is confined to the intervillus pockets. New cells produced in the pockets take about 4 days to migrate out to the tips of the villi, where they die. We have generated monoclonal antibodies to identify the absorptive and secretory cells in the epithelium, and we have used these antibodies to examine the part that Delta-Notch signalling plays in producing the diversity of intestinal cell types. Several Notch receptors and ligands are expressed in the gut. In particular, the Notch ligand DeltaD (Delta1 in the mouse) is expressed in cells of the secretory lineage. In an aei mutant, where DeltaD is defective, secretory cells are overproduced. In mind bomb (mib), where all Delta-Notch signalling is believed to be blocked, almost all the cells in the 3-day gut epithelium adopt a secretory character. Thus, secretory differentiation appears to be the default in the absence of Notch activation, and lateral inhibition mediated by Delta-Notch signalling is required to generate a balanced mixture of absorptive and secretory cells. These findings demonstrate the central role of Notch signalling in the gut stem-cell system and establish the zebrafish as a model for study of the mechanisms controlling renewal of gut epithelium.
Key words: Intestine, DeltaD, DeltaC, Notch, mind bomb, Zebrafish, Monoclonal antibody, Stem cells, Goblet cells, Enteroendocrine cells, Absorptive cells
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