Genes controlling hypothalamic development and sexual differentiation

Steroid hormones dramatically influence the development of numerous sites in the nervous system. Basic mechanisms in neural development provide foci for understanding how factors related to sex can alter the ontogeny of these regions. Sex differences in neurogenesis, cell migration, cell differentiation, cell death, and synaptogenesis are being addressed. Any and all of these events serve as likely targets for genetic or gonadal steroid-dependent mechanisms throughout development. Although the majority of sexually dimorphic characteristics in brain have been described in older animals, many hormonal mechanisms that determine sexually differentiated brain characteristics occur during critical perinatal periods. Genes suggested to contribute to the development of specific hypothalamic nuclear groups have rarely been examined in the context of sex. The identification of sex differences in the expression of some of these genes may suggest early and likely transient molecular events that set the stage for later amplification by hormone actions. Sex differences in the positioning of cells in the developing hypothalamus further suggest that cell migration may be one key target for early gene actions that impact long-term susceptibility to brain sexual differentiation.