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First published online 13 September 2006
doi: 10.1242/dev.02537

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A dynamic expression survey identifies transcription factors relevant in mouse digestive tract development

Michael Y. Choi^1,2,3, Anthony I. Romer¹, Michael Hu¹, Maina Lepourcelet^1,3, Ambili Mechoor^1,3, Ayce Yesilaltay⁴, Monty Krieger⁴, Paul A. Gray^1,5,* and Ramesh A. Shivdasani^1,3,6,

¹ Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
² Massachusetts General Hospital, Department of Medicine, 55 Fruit Street, Boston, MA 02114, USA.
³ Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
⁴ Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
⁵ Department of Neuroscience, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
⁶ Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.

Author for correspondence (e-mail: ramesh_shivdasani{at}dfci.harvard.edu)

Accepted 18 July 2006

Tissue-restricted transcription factors (TFs), which confer specialized cellular properties, are usually identified through sequence homology or cis-element analysis of lineage-specific genes; conventional modes of mRNA profiling often fail to report non-abundant TF transcripts. We evaluated the dynamic expression during mouse gut organogenesis of 1381 transcripts, covering nearly every known and predicted TF, and documented the expression of approximately 1000 TF genes in gastrointestinal development. Despite distinctive structures and functions, the stomach and intestine exhibit limited differences in TF genes. Among differentially expressed transcripts, a few are virtually restricted to the digestive tract, including Nr2e3, previously regarded as a photoreceptor-specific product. TFs that are enriched in digestive organs commonly serve essential tissue-specific functions, hence justifying a search for other tissue-restricted TFs. Computational data mining and experimental investigation focused interest on a novel homeobox TF, Isx, which appears selectively in gut epithelium and mirrors expression of the intestinal TF Cdx2. Isx-deficient mice carry a specific defect in intestinal gene expression: dysregulation of the high density lipoprotein (HDL) receptor and cholesterol transporter scavenger receptor class B, type I (Scarb1). Thus, integration of developmental gene expression with biological assessment, as described here for TFs, represents a powerful tool to investigate control of tissue differentiation.

Key words: Transcription factor, Organogenesis, Differentiation, Isx, Stomach, Intestine, Mouse

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