Home

Our long term goal is to understand the fundamental gene regulation circuitries that control neural differentiation and sub-type specification during central nervous system (CNS) development. Elucidation of these mechanisms should provide insights into the basic principles involved in the proper formation of the nervous system, as well as provide practical information for applications of regenerative medicine and treatments of CNS related diseases and traumas.

Background and Questions
The CNS of vertebrates develops from a pool of highly plastic neural stem cells (NSCs) that proliferate, acquire regional identities and generate a progressively restricted repertoire of cell types, first neurons and later oligodendrocytes and astrocytes. To achieve this mode of neural differentiation, the early neural tube is patterned by extrinsic signals that activate hierarchies of transcription factors expressed in a spatiotemporal and cell-specific manner. These transcription factors act to subdivide the neural tube into defined progenitor domains with restricted developmental potentials and subsequently establish distinct differentiation programs in the neurons and glial cells that emerge from each domain. Current evidence suggests that progression of NSCs towards neuronal differentiation is tightly linked with cell cycle control and that the two events are coordinately regulated. The molecular machinery that couples cell cycle control with neuronal differentiation remains largely unknown. A central player in these developmental events is Notch signaling. Activation of Notch1 signaling in NSCs induces self-renewal and inhibits neurogenesis. Upon neuronal differentiation, NSCs overcome this inhibition, express proneural genes to induce Notch ligands and activate Notch1 in neighbouring NSCs. However, the molecular mechanism that coordinates Notch1 inactivation with initiation of neurogenesis remains elusive.

Research Goals

• Understand the molecular mechanism that regulates Notch1 signaling in NSCs during neuronal differentiation
• Elucidate the role of Prox1 in regulating neuronal sub-type specification during CNS development
• Investigate the role of orphan nuclear receptor NR5A2 in neuronal differentiation and specification
• Identify genes that regulate proliferation, differentiation and apoptosis of neuroblastoma cancer cells

Image 1: Neural stem cells from the spinal cord of mouse embryo were grown in vitro and stained for Nestin (Red), Prox1 (Green) and Nucleus (Blue).
 

Image 2 : A section from the spinal cord of mouse embryo (E10) was stained for various molecular markers with Green, Red and Blue fluorescent antibodies.

Image 3 : Immunofluorescent detection of progenitor cells for motor neurons (Red) and interneurons (Green) in the neural tube of chick embryo.


Image 7 : The neurons of a developing mouse brain (E12) were stained yellow.