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First published online July 21, 2003
doi: 10.1242/10.1242/dev.00600

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Development 130, 3917-3928 (2003)
Copyright © 2003 The Company of Biologists Limited

nil per os encodes a conserved RNA recognition motif protein required for morphogenesis and cytodifferentiation of digestive organs in zebrafish

Alan N. Mayer1,2,* and Mark C. Fishman1,{dagger}

1 Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
2 Pediatric Gastroenterology Unit, Deptartment of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA

* Author for correspondence (e-mail: mayer{at}cvrc.mgh.harvard.edu)

Accepted 14 May 2003

Digestive organ development occurs through a sequence of morphologically distinct stages, from overtly featureless endoderm, through organ primordia to, ultimately, adult form. The developmental controls that govern progression from one stage to the next are not well understood. To identify genes required for the formation of vertebrate digestive organs we performed a genetic screen in zebrafish. We isolated the nil per os (npo) mutation, which arrests morphogenesis and cytodifferentiation of the gut and exocrine pancreas in a primodial state. We identified the npo gene by positional cloning. It encodes a conserved protein, with multiple RNA recognition motifs, that is related to the yeast protein Mrd1p. During development npo is expressed in a dynamic fashion, functioning cell autonomously to promote organ cytodifferentiation. Antisense-mediated knockdown of npo results in organ hypoplasia, and overexpression of npo causes an overgrowth of gastrointestinal organs. Thus, npo is a gene essential for a key step in the gut morphogenetic sequence.

Key words: Zebrafish, Genetics, Intestine, Digestive system, Embryology, RNA-binding proteins


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© The Company of Biologists Ltd 2003