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Molecular Biology Program and Division of Biological Sciences, University of Missouri, Columbia, MO 65211, USA
*Author for correspondence (e-mail: RiddleD{at}missouri.edu)
Accepted 11 October 2001
The daf-9 gene functions to integrate transforming growth factor-ß and insulin-like signaling pathways to regulate Caenorhabditis elegans larval development. Mutations in daf-9 result in transient dauer-like larval arrest, abnormal reproductive development, molting defects and increased adult longevity. The phenotype is sterol-dependent, and dependent on the activity of DAF-12, a nuclear hormone receptor. Genetic tests show that daf-9 is upstream of daf-12 in the genetic pathways for larval development and adult longevity. daf-9 encodes a cytochrome P450 related to those involved in biosynthesis of steroid hormones in mammals. We propose that it specifies a step in the biosynthetic pathway for a DAF-12 ligand, which might be a steroid. The surprising cellular specificity of daf-9 expression (predominantly in two sensory neurons) supports a previously unrecognized role for these cells in neuroendocrine control of larval development, reproduction and life span.
Key words: Cytochrome P450, Dauer formation, Aging, daf-9, daf-12, TGF-ß, Insulin
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