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DAF-5 is a Ski oncoprotein homolog that functions in a neuronal TGFβpathway to regulate C. elegans dauer development

2003; The Company of Biologists; Volume: 131; Issue: 2 Linguagem: Inglês

10.1242/dev.00922

1477-9129

Li S. da Graca, Karen K. Zimmerman, Melissa C. Mitchell, Marianne Kozhan-Gorodetska, Kamila Sekiewicz, Yairani Morales, Garth I. Patterson,

FOXO transcription factor regulation

An unconventional TGFβ 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 TGFβ 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.