Jurgen Knoblich (IMBA) 2: Modeling Human Brain Development in 3D Organoid Culture

#part-2 Asymmetric cell division (in which two different daughter cells are formed) is critical during human brain development. Dr. Knoblich explains how the fate of each daughter cell is determined. Part 1: Asymmetric Cell Division: From Drosophila to Humans: Asymmetric cell division is critical during embryogenesis, including for human brain development. How is this important process determined? Part 2: Modeling Human Brain Development in 3D Organoid Culture: Knoblich’s lab has developed cerebral organoids that mimic early human brain development and can be used to model brain development and disease. Talk Overview: Dr. Knoblich begins his talk by explaining the key role that asymmetric cell division plays in development of the human brain.  During mammalian brain development, neuronal progenitor cells initially divide symmetrically to increase their numbers.  Later they divide asymmetrically to produce one progenitor cell and one (or two) cells which will terminally differentiate to become neurons.  What determines which daughter cell will become which? Working in Drosophila, Knoblich and others elucidated a signaling pathway in which Par proteins are asymmetrically localized before cell division. This recruits a complex of proteins which defines the orientation of the mitotic spindle and causes the localization of Numb protein at one pole of the cell. Upon cell division, only one daughter cell will inherit Numb protein and this ultimately will determine the fate of the daughter cells.  Interestingly, this signaling pathway is conserved from insects to mammals, however, Knoblich found an important difference that may explain why humans have many more cortical neurons than mice.   In his second talk, Knoblich describes experiments in his lab to develop 3 dimensional brain organoids from human pluripotent stem cells. While studying the development of rodent brains has proved extremely useful, there are some important developmental differences that require human tissue for investigation.  In addition, some diseases such as microcephaly cannot be modeled in mice.  Knoblich and his colleagues have developed cerebral organoids that mimic early human brain development and can be used to model neurodevelopmental disorders.  They have also been able to generate separate organoids from various regions of the human brain and then fuse them and follow the migration of live neurons between these parts, opening the path to many more studies of neuronal development. Speaker Biography: Jürgen Knoblich is a senior scientist and deputy director of the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) and an Adjunct Professor at the Medical University of Vienna.  Knoblich’s lab is interested in understanding how the complexity of the human brain is generated from progenitor and stem cells during development. To address this question, they study brain development in Drosophila, mice and in 3D human stem cell derived brain organoids. Knoblich completed his PhD studies in the Friedrich Miescher Laboratory of the Max Planck Institute in Tubingen, Germany.  He was a post-doctoral fellow at the University of California, San Francisco before returning to Europe in 1997 to join the Institute for Molecular Pathology in Vienna.  In 2004, Knoblich moved to the IMBA, becoming Deputy Director in 2005. Knoblich is an elected member of the Austrian Academy of Sciences and the EMBO Council.  He has received numerous awards for his research including the Wittgenstein Prize, the Schroedinger Award and the Sir Hans Krebs Medal.   Learn more about Knoblich’s research here: