The focus of research in our laboratory is to elucidate how neurons establish individual identity in the developing nervous system and why only specific neuron subtypes are vulnerable in the neurodegenerative diseases. We tackle these questions via studying non-coding RNAs and their roles in motor neuron generation and degeneration.
Neural patterning relies on transcriptional cross-repressive interactions that ensure unequivocal assignment of neural progenitor identity to proliferating cells. We have shown previously that a specific miRNA mir-17-3p participates in Olig2/Irx3 bistable loop to carve pMN/p2 boundary. Yet if other miRNAs might regulate the expression of transcription factor to fine tune dorso-ventral pattering of the spinal cord is still unclear. In addition, the recent studies reveal that with cross-repressive interaction between pairs of Hox family proteins, motor neurons acquire subtype identities along the rostrocaudal axis. We are interested in examining if any miRNA helps to shape the boundary of motor columns. By taking advantage of the power to differentiate ES derived motor neurons in ample quantity and the ease to do genetic manipulation in mouse embryos, we are probing the global functions of miRNAs and their roles in pattering of the spinal cord.
Embryonic stem cells are regarded as the Holy Grail to be ultimately applied to incurable neurodegenerative diseases such as amyotrophic lateral sclerosis and Parkinson's disease. The first step towards this goal is to establish a robust protocol to get homogenous quantity of pure neuron subtypes affected in these diseases. With the identification of non-coding RNAs in each motor neuron subtype, we hope to incorporate these functional ncRNAs and establish an enhanced ES derived motor neuron method. Finally, we are also collaborating with several international laboratories to study potential non coding RNA pathology in spinal muscular atrophy and amyotrophic lateral sclerosis by mouse ES cell differentiation approach.