Symposium 1: Genetic and Epigenetic Influences on Brain Development and Behavior, and Their Importance for Understanding Childhood Psychiatric Disorders
Co-Chairs: Bradley S. Peterson, M.D., Jean A. Frazier, M.D., Bennett L. Leventhal, M.D.
Presenters: John Rubenstein, M.D., Ph.D., Chris Walsh, M.D., Ph.D., Michael Meaney, Ph.D., Eric Lander, Ph.D.
Tuesday, October 23
7:00 – 10:00 p.m. (open)
Sponsored by the AACAP Work Group on Research
The Founders of the Research Initiative Symposium is designed to bring to the practicing clinician and academician a review and discussion of advanced scientific techniques and how they are relevant to the contemporary clinical practice of child and adolescent psychiatry.
Genetic Control of Prefrontal Cortex Development
John L. R. Rubenstein, M.D., Ph.D. is the Nina Ireland Distinguished Professor in Child Psychiatry at University of California, San Francisco. Dr. Rubenstein is a leader in elucidating genetic mechanisms that control patterning and differentiation of the embryonic mouse forebrain. He identified key genes and processes that define distinct progenitor domains that generate specific programs of neurogenesis, cell migration, and connectivity.
Dr. Rubenstein reviews studies on the mechanisms that control patterning and differentiation in the mouse cerebral cortex. His work has focused on the role of FGF-signaling in controlling the size and nature of the frontal cortex. He provides evidence that Fgf8 has a global role in patterning rostral parts of the cortex, whereas other Fgf genes, such as Fgf17, have a selective role in regulating development of the frontal cortex subdivisions. These studies provide insights into a signaling pathway that is required for generation of part of the brain that regulates important executive functions, and suggest that defects in this pathway could underlie some forms of human neuropsychiatric disorders.
Genetic and Genomic Studies of Patterning in the Human Cerebral Cortex
Chris Walsh, M.D., Ph.D. is Bullard Professor of Neurology at Harvard Medical School, Chief of the Division of Genetics at Boston Children’s Hospital, Director of the Harvard-MIT M.D.-Ph.D. program, and an Investigator of the Howard Hughes Medical Institute at Beth Israel Deaconess Medical Center. Dr. Walsh has studied patterns of neural stem cell division, cell fate choices, and cell migrations in the developing cerebral cortex, and has pioneered the analysis of human genetic diseases that disrupt the cerebral cortex.
Dr. Walsh discusses his studies of genetic influences on the asymmetric patterning of the human cerebral cortex that may subserve lateralized functions of the cerebral hemispheres. Genetic malformations of human cerebral cortex can affect different cortical regions preferentially, potentially identifying genes involved in generating area-specific patterns in human cortex. Dr. Walsh reviews the substantial numbers of genes he has discovered that have differing levels of expression across the left and right hemispheres early in human gestation and the effects that these differing levels of expression have on cortical patterning.
Variations in Maternal Care Produces Stable Phenotypic Variation in Stress Responses Associated with Epigenetic Programming of Transcriptional Sites
Michael Meaney, Ph.D. is currently James McGill Professor of Medicine, full professor in the Departments of Psychiatry and Neurology and Neurosurgery, and Director of the Sackler Program for Epigenetics and Psychobiology, McGill University and Douglas University Mental Health Institute, Montreal, Canada. Dr. Meaney’s particular interest is in the mechanisms by which adversity in early life might alter neural development so as to render certain individuals at risk for pathology later in life.
Maternal care alters the development of adaptive behavioral and endocrine responses to stress in the rat, an example of maternally regulated, phenotypic plasticity. Dr. Meaney reviews the mechanisms for these maternal effects which involve stable changes in the expression of genes in the offspring in brain regions that mediate stress reactivity, as well as regions involved in the processing of information related to the stressor. These include effects on systems that regulate central corticotrophin-releasing factor (CRF) synthesis and release from the hypothalamus and amygdala. These studies suggest the presence of experience-dependent plasticity that benefits the offspring by establishing alternative phenotypes that more successfully match the demands of their particular environmental niche.
Genomics and the Future of Medicine: Beyond the Human Genome Project
Eric S. Lander, Ph.D. is founding director of the Broad Institute. As one of the principal leaders of the Human Genome Project, he and his colleagues are using these findings to explore the molecular mechanisms underlying the basis of human disease. Over the past 15 years, Lander and colleagues have developed many of the key tools and generated many of the key information resources of modern mammalian genomics. Their work includes: mapping and sequencing of the human, mouse, and other genomes; understanding the functional elements encoded in genomes through comparative analysis; understanding the genetic variation in the human population and its relationship to disease susceptibility; understanding the distinctive cellular signatures of diseases and of response to drugs; and understanding the mutations underlying cancer.
Details on Dr. Lander’s presentation are coming soon.
