(1) Development of nuclear brain structure
Mammalian brain consists of both laminar (e.g. neocortex and retina) and nuclear (e.g. thalamus, hypothalamus and brain stem) structures, which directly affect behavior and cognition. Very little is known about spatial organizational principles of nuclear brain structures at single-cell level, in contrast to well-studied stratified neocortex. We are using single-cell analysis approach such as clonal analysis (single-cell lineage tracing), single-cell RNAseq and single-cell genetic deletion to investigate the behavior of embryonic neural stem cells; the generation, migration and connection of neurons in hypothalamus and brain stem; and the molecular and cellular mechanisms underlying congenital neural disease.
(2) Neural control of metabolic disorders
With the improvement of material living conditions, obesity has become a significant public health concern affecting more than half a billion people worldwide. Multiple hypothalamic nuclei and their associated neural circuits play an important role in regulating human feeding and body metabolism. On the one hand, we are identifying the novel neuronal ensemble involved in regulating feeding behavior and body metabolism. One the other hand, we are intrigued by the features and functions of tanycytes, the putative hypothalamic stem cells.
More specifically, we are focusing on the role of adult neural stem cells (NSCs) in regulating aging and obesity as well as the potential mechanisms. Canonical adult NSCs reside in the subventricular zone (SVZ) lining lateral ventricle and the subgranular zone (SGZ) within hippocampus and decay during the aging process. Recently, it has been reported that adult hypothalamic NSCs regulate feeding behavior, metabolic disorders and systemic ageing. We will use lineage tracing approach to investigate the behavior of adult hypothalamic NSCs under distinct environmental context and its effect on organismal metabolism. Furthermore, we are also interested in the incorporation of hypothalamic new-born neurons in neural circuit.
(3) Homeostatic regulation of neural stem cells
Homeostasis maintenance of neural stem cells is critical for neural development and neural injury regeneration. Dysregulation of embryonic NSC homeostasis cause neural developmental disorders, such as autism and intellectual disability. Disruption of adult NSC homeostasis may result in schizophrenia, mood disorder and progeria. We are using lineage tracing and genomic editing approaches to investigate the molecular mechanisms underlying homeostatic regulation of NSCs under physiological and pathological conditions.