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First published online 17 December 2003
doi: 10.1242/dev.00922

Development 131, 435-446 (2004)
Published by The Company of Biologists 2004
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DAF-5 is a Ski oncoprotein homolog that functions in a neuronal TGFß pathway to regulate C. elegans dauer development

Li S. da Graca1, Karen K. Zimmerman1, Melissa C. Mitchell1, Marianne Kozhan-Gorodetska1, Kamila Sekiewicz1, Yairani Morales1 and Garth I. Patterson,,1,2,*

1 Department of Biochemistry and Molecular Biology, Rutgers University, Piscataway, NJ 08854, USA
2 Cancer Institute of New Jersey, New Brunswick, NJ 08853, USA

* Author for correspondence (e-mail: patterson{at}mbcl.rutgers.edu)

Accepted 30 September 2003

An unconventional TGFß superfamily pathway plays a crucial role in the decision between dauer diapause and reproductive growth. We have studied the daf-5 gene, which, along with the daf-3 Smad gene, is antagonized by upstream receptors and receptor-regulated Smads. We show that DAF-5 is a novel member of the Sno/Ski superfamily that binds to DAF-3 Smad, suggesting that DAF-5, like Sno/Ski, is a regulator of transcription in a TGFß superfamily signaling pathway. However, we present evidence that DAF-5 is an unconventional Sno/Ski protein, because DAF-5 acts as a co-factor, rather than an antagonist, of a Smad protein. We show that expressing DAF-5 in the nervous system rescues a daf-5 mutant, whereas muscle or hypodermal expression does not. Previous work suggested that DAF-5 and DAF-3 function in pharyngeal muscle to regulate gene expression, but our analysis of regulation of a pharynx specific promoter suggests otherwise. We present a model in which DAF-5 and DAF-3 control the production or release of a hormone from the nervous system by either regulating the expression of biosynthetic genes or by altering the connectivity or the differentiated state of neurons.

Key words: Dauer, Cyclin dependent kinase inhibitor, Dachshund box, Nematode


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