Transcriptional Control of Cortical Development - A Link to Autism
We are pleased to welcome John Rubenstein, MD, PhD to the University of Pittsburgh as our special guest to present the Irene Jakab Lecture this year.
Dr. Rubenstein trained in Chemistry, Biophysics, Medicine and Psychiatry at Stanford and Developmental Biology at the Pasteur Institute. He spent his faculty career at UCSF where he has been studying the genetic mechanisms that divide the mammalian forebrain into regions and layers and allocate distinct neuronal types to each domain. Over 30 years ago he discovered transcription factors that control the topological organization of embryonic forebrain, Dlx-2 and Tbr-1. He also analyzed others (e.g., Gsx-1 and -2, and Nkx-2.1, -2.2, and -6.2) that specify CNS dorsoventral subdivisions. Further analysis of the Dlx genes led to the discovery that cortical inhibitory neurons are generated in the ganglionic eminences and migrate tangentially to cortex, with Dlx controlling their migration, function and transmitter choice. Searching downstream, he elucidated molecular pathways that control migration and fate specification, including downstream transcription factors (e.g., Couptf1,2, Npas1,3, Lhx6,8), chemokine signaling (e.g., Cxcr4,7), and morphogens (e.g., Shh). Continued analysis of regionalization demonstrated the existence of patterning centers in the embryonic forebrain that regulate cortical arealization through the expression of Fgf8, 15 and 17, which induce and repress transcription factors to specify the size of cortical subdivisions. Most recently, Dr. Rubenstein extended the work to a still deeper level, working at the whole genome level to identify enhancer elements to which transcription factors bind, governing gene expression in specific regions and cell types throughout the cortical protomap. Together, this work has led to a deep understanding of mammalian forebrain development, and is providing insights into causes of autism (e.g., Tbr1 mutations) and new approaches to treatment (e.g., interneuronal transplantation for epilepsy).
Date & Time. Friday, October 9, 2020 12:00pm to 1:30pm
Location. UPMC Western Psychiatric Hospital (WPH) Auditorium. This lecture will be offered as a live stream in the event that COVID-19 safety regulations prevent in person attendance at the lecture.
Learning Objectives. At the conclusion of this lecture participants will be able to:
- Describe the basic steps in cortical development.
- Understand what the Tbr1 transcription factor does.
- Conceptualize how Tbr1 may contribute to autism.
The entirety of this program will be a lecture by the speaker(s). All individuals able to control the content of this educational activity are required to disclose all relevant financial relationships with any proprietary entity producing, marketing, re-selling, or distributing health care goods or services, used on, or consumed by, patients. Registration is not required for this event. This event is free and there will be no refunds. The University of Pittsburgh is an affirmative action, equal opportunity institution.
For More Information. Please contact Frances Patrick (firstname.lastname@example.org).