Additional session summaries will be added shortly.
Neural stem-progenitor cells in the embryonic, early postnatal, and adult mammalian brain
Significant advances have been made in our understanding of the regulation of neural stem-progenitor cell (NSC) fate during development of the mammalian brain as well as in adulthood. Embryonic NSCs divide frequently and generate a wide variety of neuronal and glial cell types that constitute the mature brain. In contrast to the widespread production of glial cells that continues in the postnatal brain, the production of neurons ceases by the completion of brain development—with the exception of that in two neurogenic niches, the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampal dentate gyrus. This session focuses on regulation of the fate of embryonic, early postnatal, and adult NSCs through intrinsic and extrinsic mechanisms.
Cell lineage and neural diversity in the cerebral cortex
The cerebral cortex is responsible for all higher-order brain functions, such as sensory perception, motor control, and cognition. It contains a vast number of cells that exhibit an extraordinary diversity in molecular, cellular, and functional features. Since the ground-breaking work of Ramon y Cajal, cortical cell types have been increasingly defined by their location, neurotransmitter type, morphology, gene expression, and synaptic connectivity. The ability to observe accurately and manipulate precisely cortical activity depends on greater knowledge of diverse neural types. While extensive efforts such as single cell transcriptome analysis have been taken to provide an accurate census of cell types in the cortex, the origins of neural diversity in the cortex remain poorly understood. It is likely, at least to a certain degree, that cortical neural diversity is rooted in the process of neurogenesis and gliogenesis during early development. For example, it is well-established that excitatory glutamatergic principal neurons and inhibitory GABAergic interneurons in the cortex are originated from distinct progenitors. However, the intricate relationship between cell lineage and neural diversity is only beginning to come into focus. In this symposium, the speakers will present and discuss ongoing researches related to cell lineage and neural diversity in the cerebral cortex.
This session focuses on the interactions of oligodendrocytes and neurons during CNS development. The issues of axonal signaling to differentiating oligodendrocytes and signaling from myelinating oligodendrocytes to neurons will be presented. Dr. Kazuhiro Ikenaka will discuss the mechanisms of myelination by a single oligodendrocyte, when in the presence of active axons and inactive axons. Thus, will a single oligodendrocyte preferentially myelinate active axons over inactive ones? It is known that myelin sheath length is longer on active axons. Will a single oligodendrocyte form longer internodes on active axons and shorter internodes on inactive ones? Dr. Wendy Macklin will discuss the signaling between oligodendrocytes and axons that enhance myelination, studying a model in which gene expression in cortical neurons is altered. These studies address what changes occur in the axons and in the oligodendrocytes, which start to differentiate and then die. Dr. Kelly Monk will discuss studies on a recently completed large-scale, three-generation forward genetic screen in zebrafish to discover mutants with defects in myelinated axon development. This highly successful screen uncovered 28 new mutants, many of which identify genes with no previously defined functions in glial cells. One of the most interesting oligodendrocyte mutants will be discussed. Dr. Eva-Maria Albers will discuss activity-dependent transfer of extracellular vesicles termed exosomes from oligodendrocytes to neurons, and its relevance for neuronal homeostasis and glial support. A transgenic reporter model to study exosome transfer in vivo allows investigation of the functional competence of exosomes released from proteolipid protein- or 2’,3’ cyclic nucleotide phosphodiesterase-deficient oligodendrocytes.
Modeling neurodevelopment and developmental brain disorders: from Primate to human PSC-based 2D and 3D models
Recent advancement in deriving pluripotent stem cells from humans and genome engineering technology to genetically edit the primate and human genome made it possible to develop primate and human model systems to address biological questions. This session will provide the audience an updated view of how these state-of-the-art technologies are applied to understand organogenesis and to decipher the pathology and molecular mechanisms underlying disorders, with an emphasize in the brain development and neurological disorders. Dr. Pierre Vanderhaeghen, a Professor at University of Brussels will talk about species-specific mechanisms of human cortical neurogenesis. Dr. Orly Reiner, a professor at Weizmann Institute Israel will discuss her work using human brain organoids on a Chip to model brain development and disease. Dr. Ming, a Professor at University of Pennsylvania, will discuss the use of 2D and 3D organoid cultures systems from human iPSC to understand the cellular impact of Zika virus infection on neurogenesis, synapse formation and underlying molecular mechanism. And Dr. Yi Sun, a Professor at University of California, Los Angeles will discuss their effort of using TALEN-edited MECP2 mutant cynomolgus monkeys to model Rett Syndrome, a devastating neurodevelopmental disorder with no cure.