Neural Stem Cells & Neurogenesis

Mechanisms regulating neural stem cells and neurogenesis

Adult hippocampal neurogenesis reflects a remarkable form of structural plasticity in the mature mammalian brain. Fully characterizing this phenomenon could have far-reaching implications for understanding hippocampal function and revealing fundamental properties of neural development and the regenerative capacity of the mammalian central nervous system. Over the past 15 years, the laboratory has systematically investigated adult hippocampal neurogenesis in mammals at the molecular, cellular, and neuronal circuit levels and reported a number of key findings that have influenced the field. Via genetic clonal analysis, we demonstrated the existence of bona fide neural stem cells in the adult mammalian hippocampus, capable of both self-renewal and multipotent fate specification of progeny. We provided a detailed blueprint about how newborn neuron integration into the existing neuronal circuitry and its underlying molecular, cellular and circuitry mechanisms. In collaboration with Dr. Guo-li Ming, we have discovered critical roles of multiple psychiatric disorder risk genes in regulating the development of newborn neurons during adult hippocampal neurogenesis. We discovered novel mechanisms whereby distinct neuronal circuits influence neural stem cell properties and the development of newborn neurons in the hippocampus. Currently, we are addressing the origin of adult neural stem cells using clonal lineage-tracing approaches and investigating mechanisms regulating adult neural stem cells and neurogenesis using mouse genetic approaches. We have also extended our analyses of neural stem cells and neurogenesis to embryonic cortex and hypothalamus in mice and in humans using brain organoids.