Statement of Benefit to California:
Year 1In this reporting period, we have been continuing our work to identify genes that regulate neural stem cells to produce different types of neurons in the brain.
Year 2In the past grant period, we have identified Tbr1 as the major cell fate-determing gene for the corticothalamic neurons.
Year 3In year 4 of the grant period, we continue to explore the molecular mechanisms that regulate neural stem cells to generate various types of cortical projection neurons, in particular the corticospinal motor neurons and the corticothalamic neurons. We have identified a novel transcription factor that regulates neural stem cell differentiation.
Year 4During the last grant period, we continue to explore the molecular mechanisms that regulate neural stem cells to generate different types of neurons in the mammalian brains. We have identified a transcription factor that is essential for neural stem cell differentiation, neuronal migration and axon projection.
Year 5We have continued our study to identify the molecular mechanisms that regulate cortical neuron fate specification. We have discovered/confirmed that (1) Early cortical progenitors are multipotent, and they give rise to different types of cortical project neurons and glia based on birthdates. There is no evidence of intrinsically lineage-restricted early neural stem cells; (2) expression of Fezf2, a major cell fate determining gene for cortical neurons, is regulated by multiple enhancers and promoters. These enhancers and promotor region have distinct and sometimes overlapping activity; (3) transcription factor Nfib is essential for the differentiation of neural stem cells and required for the cortical neurons to extend corticofugal axons; and (4) splicing factor Tra2b is essential for the survival and differentiation of cortical neural progenitor cells. These results provide novel insights into the development of cortical neurons.