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First published online 19 October 2005
doi: 10.1242/dev.02102

Development 132, 5043-5054 (2005)
Published by The Company of Biologists 2005
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mab-2 encodes RNT-1, a C. elegans Runx homologue essential for controlling cell proliferation in a stem cell-like developmental lineage

Rachael Nimmo1, Adam Antebi2 and Alison Woollard1,*

1 Genetics Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
2 Huffington Center on Ageing and Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Room M-320, Houston TX 77030, USA

* Author for correspondence (e-mail: alison.woollard{at}bioch.ox.ac.uk)

Accepted 15 September 2005

In this report, we demonstrate that C. elegans mab-2 mutants have defects in the development of a male-specific sense organ because of a failure in the proliferation of the stem cell-like lateral hypodermal (seam) cells. We show, by positional cloning, that mab-2 encodes RNT-1, the only C. elegans member of the Runx family of transcriptional regulators, which are postulated to act both as oncogenes and tumour suppressors in mammalian cells. Importantly, we find that rnt-1 is a rate-limiting regulator of seam cell proliferation in C. elegans, as overexpression of rnt-1 at particular developmental stages is capable of driving extra cell divisions, leading to seam cell hyperplasia. Loss of rnt-1 is correlated with upregulation of cki-1, a CDK inhibitor. Deregulated expression of Runx genes in humans is associated with various cancers, particularly leukaemias, suggesting a conserved role for Runx genes in controlling cell proliferation during development, especially in stem cell lineages. C. elegans is therefore an important model system for studying the biology, and oncogenic potential, of Runx genes.

Key words: Caenorhabditis elegans, Runx genes, Cell proliferation, Male tail development


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H. Kagoshima, R. Nimmo, N. Saad, J. Tanaka, Y. Miwa, S. Mitani, Y. Kohara, and A. Woollard
The C. elegans CBF{beta} homologue BRO-1 interacts with the Runx factor, RNT-1, to promote stem cell proliferation and self-renewal
Development, November 1, 2007; 134(21): 3905 - 3915.
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