Art
Arnold
Laboratory
UCLA Department of Physiological Science Box
951606 Los Angeles, CA 90095-1606 (310)825-9340
Description of Research
We study factors that lead to sex differences in development of the brain. Early in life, male and female brains diverge in their patterns of development, and they remain different in their function and susceptibility to disease. Over the last 40 years a great deal of experimental evidence has proven that secretions of the gonads are critical for causing these sex differences. For example, the testes of fetal male mammals secrete testosterone, which acts on the brain to make it form masculine brain circuits. In females testosterone levels are much lower, which allows feminine development. Yet our research over the last decade has suggested that not all sex differences in the brain are the result of steroid action. Our hypothesis is that XX and XY cells differ structurally and functionally because of the action of X and Y genes intrinsic to the cells.
Mice We compare the brains and behavior of mice that differ in the genetic sex of brain sex (XX vs. XY) but which have the same type of gonad, either testes or ovaries. Our research gives information about how the X and Y genes cause sex differences in brain cells, in addition to the well-known sex-specific effects of gonadal hormones. We also study the patterns of expression of X and Y genes in the brain.
Songbirds In zebra finches, males sing a courtship song not sung by females. The neural circuit for song in males is much larger than that of females. Our research indicates that these sex differences in the brain are caused by the effects of sex chromosome genes within brain cells. For example, genetic females who have testes nevertheless develop a feminine neural song system. We study the genes encoded by the sex chromosomes, and their patterns of expression in the brain, and aim to find the genes that make the difference between male and female brain cells.
Highlights
We recently studied a half-male, half-female zebra finch (Agate et al., 2003). This bird had male feathers and a testis on the right half of its body, and female feathers and an ovary on the left half. The brain was genetically male on the right and genetically female on the left. The bird represents, therefore, the unusual situation in which genetically male and female brain cells developed in the same gonadal hormone environment, so that differences in these cells can be attributed to their genetic makeup, not to the hormones. The neural song circuit on the right (male) half of the brain was, in fact, more masculine than the circuit on the left (female) half. This result is strong support for the idea that the sex chromosome genes within brain cells play an important role in making the brain masculine or feminine.
We have recently found that mouse XY and XX midbrain cells differ in their behavior in vitro irrespective of the gonadal hormones present in their environment (Carruth et al., 2002). That is, cultures containing XY cells, taken from embryos with testes or ovaries, developed more dopamine neurons than cultures with XX cells taken from embryos with testes or ovaries. The result suggests that expression of X or Y genes within the brain cells contributes to the sex difference in behavior of the cells.
We have compared sexually dimorphic behavioral and brain phenotypes in XX vs. XY males, and XX vs. XY females (De Vries et al., 2002). Although most of the sex differences tested so far appear to be explained by sex differences in gonadal secretions, one dimorphism is partly explained by differences in sex chromosomes contained within the brain cells themselves. The density of vasopressin fibers in the lateral septum is higher (more masculine) in XY males than in XX males, and higher in XY females than in XX females.
Publications
Please see Pub Med
Current Members of the Arnold Lab
Related UCLA Resources
Related WWW Resources
Zebra Finch cDNA, EST, and genome resources