Description of Research

We study factors that lead to sex differences in tissue function, especially in 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. The classic dogma of sexual differentiation states that all somatic sex differences are caused by gonadal hormones, which differ in the two sexes over the lifespan. Our research indicates that the classic dogma is incomplete. Some sex differences are the result of direct action of genes encoded on the sex chromosomes, not the result of steroid hormone action. XX and XY cells differ functionally because of the action of X and Y genes intrinsic to the cells.

Mice
Working with numerous other groups, we have developed a novel mouse model for studying sex chromosome effects leading to sex difference in traits. We compare the mice that differ in the genetic sex of cells (XX vs. XY) but which have the same type of gonad, either testes or ovaries. We find that XX and XY mice of the same gonadal sex differ with respect to their susceptibility to disease, and in their brain and behavioral traits.

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.

Sex chromosome dosage compensation in birds
Species with XX/XY sex chromosome systems (XY heterogametic male) show evidence of effective X chromosome dosage compensation, in which one sex has evolved an X chromosome-wide mechanism that adjusts the expression of X genes to match that of the other sex. Birds have ZZ/ZW sex chromosomes (ZW heterogametic female). We have found that birds surprisingly lack an effective mechanism of Z chromosome mRNA dosage compensation analogous to XX/XY systems. A restricted region of the Z chromosome, however, shows signs of coordinated dosage compensation. The bird model challenges long-standing ideas regarding the supposed requirement for effective dosage compensation.

Publications

Please see Pub Med

Current Members of the Arnold Lab

• Hector Alcala
• Arthur P. Arnold, Ph.D.
• Xuqi Chen, M.D
• William Grisham, Ph.D.
• Yuichiro Itoh, Ph.D
• Kathy Kampf
• Deepthi Sudhakar
• Rebecca Watkins

Graduates of the Arnold Lab

Related UCLA Resources

• UCLA Interdepartmental Ph.D. Program for Neuroscience
• UCLA Interdepartmental Undergraduate Program for Neuroscience
• UCLA Department of Physiological Science
• UCLA Brain Research Institute
• UCLA Laboratory of Neuroendocrinology

Related WWW Resources

• Society for Behavioral Neuroendocrinology
• Organization for the Study of Sex Differences

Zebra Finch cDNA, EST, and genome resources

• University of Illinois Estima EST database: http://titan.biotec.uiuc.edu/cgi-bin/ESTWebsite/estima_start?seqSet=songbird
• Duke University zebra finch transcriptome database: http://songbirdtranscriptome.net/
• Proposal to construct a physical map of the genome of the zebra finch:Zebra_finch_genome_white_paper.pdf
• Proposal to sequence the genome of the zebra finch http://www.genome.gov/Pages/Research/Sequencing/SeqProposals/ZebraFinchSeq2.pdf
• Songbird Genome Website http://songbirdgenome.org/
• UCSC Zebra Finch Genome Browser http://genome.ucsc.edu/cgi-bin/hgGateway?db=taeGut1