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From the Office of Dr. David Crews
Focus of Research
Note: (numbers in parentheses indicate publication number)

2. Signal transduction and temperature-dependent sex determination (NSF IBN-9723617)

Because of its categorical nature, sex determination has become a model for understanding development in general. Further, sex determination is a case study in how evolution has produced very different mechanisms for achieving the same end. Here I take advantage of the fact that in many reptiles the sex of the offspring depends on the incubation temperature of the egg, a process known as environmental sex determination (c.f., 180, 187, and 215). One question concerns how the physical stimulus of temperature is transduced into a physiological stimulus that operates ultimately at a molecular level to determine an individual’s gonadal sex. In this work I use the red-eared slider turtle as the animal model system. I have demonstrated that sex steroid hormones are the physiological equivalent of incubation temperature, serving as the proximate trigger for male and female sex determination. Temperature appears to accomplish this end by acting on genes coding for steroidogenic enzymes (e.g., steroidogenic factor 1 and aromatase) and sex steroid hormone receptors (e.g., estrogen and androgen receptors)(e.g., 232 and 258). Phylogenetic analysis indicates that temperature-dependent sex determination is the precursor of sex determination by genotypic mechanisms (e.g., sex chromosomes). There is suggestive evidence that similar dynamics are present in mammalian and avian species but are masked by homeothermy (e.g., 192 and 215).
This work has also contributed to new paradigms for understanding sexuality (c.f., 54, 180, 191, 209, 225, 231, 251, and 254). For example, working with animals that lack sex-linked sex determining genes has reinforced the conclusion that the molecular cascades that lead to males and females are contained in each individual. That is, the species may differ in their patterns of regulation, but the genes associated with sex determination are conserved. What differs is the trigger; in some it is sex chromosomes at fertilization, in others it is environmental factors during embryogenesis, and still others it is the social context the adult might find itself. This is overturning the classic paradigm idea of an "organized and a "default" sex; rather we now regard both sexes as organized and the question now becomes why the activation of one cascade (e.g., the ovary-determining cascade) actively suppresses the complementary sex determining cascade? Further, I have put forward another paradigm to take the place of the organized-default concept, namely that the female is the ancestral sex and the male the derived sex. This leads to a new concept, namely why might males be more like females, than females are like males? The utility of this concept is becoming apparent as we continue to gather evidence for gender differences in genetic and mental disorders.