1. Investigate the role of alternative spliced forms of fibroblast growth factor 8 (Fgf8).
Fgf8 plays an important role in regulating key developmental processes such as cell proliferation, survival, migration, and differentiation. The single Fgf8 gene in both human and mouse produces multiple isoforms of variable N-termini by alternative splicing. Using the developing midbrain and hindbrain as a model system, we have demonstrated the distinct inductive activities of two major Fgf8 isoforms, Fgf8a and Fgf8b. Using gain-of-function and loss-of-function approaches, we attempt to dissect the relative contributions of Fgf8a and Fgf8b in development of the central nervous system, and the mechanisms underlying the distinct activities of these isoforms.
2. Transcriptional control of thalamic development Thalamus is responsible for the integration and processing of almost all sensory and motor information to the neocortex.
Previous and ongoing studies have demonstrated that Gbx2, which is a transcription factor, is a key regulator for differentiation and axon targeting of thalamic neurons. We seek to elucidate the molecular and cellular mechanisms underlying the function of Gbx2 in developing thalamic neurons. One of our approaches is to identify the downstream targets of Gbx2, and to investigate whether and how these candidate target molecules mediates the diverse functions of Gbx2 in thalamic development.
3. Development of efficient and reproducible methods for genetic modifications of human embryonic stem cells.
Human embryonic stem cells (hESCs) are an unlimited source of precursor cells that can be directed to differentiate into any type of cells for regenerative medicine and studies of toxicology and pharmacology. The promises of hESC applications depend on our knowledge and ability to drive hESC differentiation into particular cell type as desired. Genetic manipulations of hESCs are essential for the study of hESC biology and differentiation. We are developing efficient and reproducible methods for genetic modifications of hESCs. We will apply these new tools and reagents in order to control in vitro differentiation of hESCs.