The relationship between sex and behavior is a persistent question from society, as well as the medical and the research communities. Neuroscience research has undeniably demonstrated that the genetic sex of an individual has broad ranging effects on both anatomical brain areas and behaviors. However, a parallel line of research has demonstrated the inaccuracy of predicting phenotype based solely on genome sequence, thus implicating environmental influence. I propose to contrast the mechanisms that underlie genetic and environmental influences on gender biased behaviors using a pair-bonded monogamous animal model of parental care, genus Julidochromis, African cichlid fishes. I take a "systems biology" approach that quantitatively integrates phenotype data from multiple levels including neural gene expression, hormone titers, and behavioral observations. The African Cichlid fishes provide a unique opportunity to observe naturalistic behaviors in which gender-biased behaviors can be reversed by either environmental effects or genetic effects. The behavioral phenotypes, hormone levels, and gene expression profiles can therefore be assessed in these three paradigms 1) conventional gender-role 2) environmental reversal 3) genetic reversal. Within the conventional gender-bias paradigm the males are larger, more aggressive and territorial, while the females provide the egg care and nest maintenance. In this same species, altering the social environment, will reverse gender-biased behaviors, while in a closely related species the gender-biased behaviors are reversed by genetic background. Covariance analysis across multiple levels of phenotype will identify molecular modules that correlate with gender biased behaviors independent of sex. Paradigm 1 will be used as baseline from which to measure and contrast the two reversal phenotypes, and the molecular modules that are recruited in paradigms 2 & 3 will be contrasted in order to evaluate the mechanisms that underlie environmental and genetic influence. The localization of gender-biased neuronal gene expression will indicate neuroanatomical sites for regulation of these behaviors and thus lay the foundation for a model system in which to address the relationship of neural and molecular networks that orchestrate plastic and biased gender-role behavior. PUBLIC HEALTH RELEVANCE The great influence of sex on the brain is undeniable at the level of neuroanatomy, neurochemistry, brain function, and even behavior. The proposed systems level research integrates data from behavioral, physiological and molecular level in order to contrast mechanisms by which genes and the environment influence gender-biased behaviors and identify neuroanatomical sites important for the regulation of these behaviors. I use an animal model (cichlid fish) to study complex social behaviors that are directly relevant to the broad range of normal sex-related differences in human social behaviors as well as psychiatric conditions that show both genetic and environmental components. [unreadable] [unreadable] [unreadable]