Biology Reference
In-Depth Information
of steroid signaling has illuminated important and novel facets of metazoan
life history regulation. DAF-12 controls broad aspects of
C
.
elegans
matura-
tion, including regulation of developmental arrest at the long-lived dauer
stage, progression from second-to third-larval stage programs in develop-
mental timing circuits, and organismal longevity. DAF-12's essential role
in these processes is to couple environmental and physiologic information
to the precise timing of reproductive development. In each context, it is
embedded in a remarkably rich circuitry, whose elucidation has yielded
major insights into endocrine regulation of metazoan reproductive commit-
ments, developmental timing, and longevity. Here, the author reviews the
role of steroid receptor DAF-12 in the framework of these circuits.
2. ENDOCRINE REGULATION OF THE DAUER DIAPAUSE
2.1. C. elegans life history
All animals have the ability to sense environmental quality and nutrient
availability, and adjust rates of maturation accordingly. In favorable environ-
ments,
C
.
elegans
develops rapidly from embryo through four larval stages
(L1-L4) marked by molts to adulthood in about 3.5 days, termed reproduc-
tive development. They produce progeny for a week, and then typically live
another two weeks. In unfavorable environments marked by food scarcity,
elevated temperatures, and overcrowding indicated by ascaroside phero-
mones (
Butcher, Fujita, Schroeder, & Clardy, 2007; Golden & Riddle,
1984
), they arrest development at an alternate third larval stage called the
dauer diapause, which is specialized for survival and dispersal (
Cassada &
Russell, 1975
). Dauer larvae are arrested at a “prepubertal” quiescent state,
morphologically and metabolically distinct, highly stress resistant and long
lived, surviving over 4 months without food. Yet, when returned to favor-
able conditions they will mature into reproductive adults with a normal life
span. Although mammals do not have explicit states of diapause, they can
enter alternate metabolic states of hibernation, torpor, caloric restriction,
or maturational delay, which mimic aspects of dauer.
2.2. A hormone-regulated switch governs the dauer decision
What are the molecular pathways that govern dauer formation? Early genetic
screens identified abnormal
da
uer
f
ormation (Daf ) mutants that either enter
dauer constitutively (Daf-c) or are defective in dauer formation (Daf-d)
(
Riddle, Swanson, & Albert, 1981
). A molecular genetic analysis of the
