When conditions are harsher, however, the worm – a classic model organism frequently studied in the laboratory – does not produce the hormone and enters a special stage called the dauer diapause in which it remains an immature larva until the situation improves. In a paper that appears in the journal Developmental Cell, Baylor College of Medicine researchers led by Dr. Adam Antebi, assistant professor in the BCM Huffington Center on Aging and the department of molecular and cellular biology, identify a new gene called DAF-36 involved in making this hormone.
"Our evidence suggests that DAF-36 works early in a pathway that converts cholesterol through a series of enzymatic steps into the dafachronic acids, the active ligands for DAF-12 nuclear receptor," said Antebi. In this instance, a ligand is a molecule that binds to a specific site on a protein.
These particular ligands promote the maturation of the C. elegans reproductive capacity and prevent the organism from going into the immature long-lived larval phase called dauer diapause. Antebi and collaborators identified these ligands in a report that appeared March 24, 2006 in the journal Cell.
In addition, said Antebi, DAF-36 is required for the long life seen in forms of C. elegans that lack germline cells – those cells – like sperm and egg in animals – are necessary for reproduction.
In a related work published in Cell (Motola et al. 2006), the chemical identification of the DAF-12 ligands as steroid-like hormones is reported, providing the first evidence for steroid control of maturation in worms. Antebi speculates that this may resemble how estrogen and androgen hormones similarly govern human maturation.
Others involved in the research include: Dr. Veerle Rottiers, postdoctoral associate at BCM, Drs. Daniel L. Motoloa, Carolyn L. Cummins and David J. Mangelsdorf of The University of Texas Southwestern Medical Center in Dallas, Dr. Birgit Gerisch of Max Planck Insitute for Molecular Genetics in Berlin, and Dr. Kiyoji Nishiwaki of the RIKEN Center for Developmental Biology in Japan.
Developmental Cell