Mechanisms of neural stem cell differentiation into astrocytes through the Notch intracellular signaling pathway
Members of the basic helix-loop-helix (bHLH) transcription factors play vital roles in multiple developmental processes. In neurogenesis, several bHLH transcription factors are responsible for guiding cells to a tissue-specific fate and initiating their differentiation. N-Twist, a bHLH transcription factor, is expressed in the developing mouse and chick CNS system, specifically in the neural tube and the mesencephalon (midbrain). Currently, published literature suggests N-Twist is a transcriptional inhibitor of the neurogenic transcription factor MASH1. Thus it was predicted that N-twist would be a negative regulator of neurogenesis.
The objectives of our study were to determine the specific population of neuronal cells that express N-Twist, a bHLH transcription factor, and if N-twist positively or negatively influences the neurogenesis by neural stem cells in the developing nervous system. To detect the presence of the N-Twist gene, the in situ hybridization technique was established and optimized to detect the expression of N-twist mRNA in the developing mouse and chick. Embryos were harvested and sectioned at different developmental stages. We found that N-twist was expressed in the floorplate region of the spinal cord and midbrain. This region is primarily composed of a group of cells that are responsible for determining the final fate of neural cells and giving rise to glia. To address the second question, N-Twist was over expressed in the developing neural tube and the mesencephalon using in ovo electroporation. We determined that N-twist overexpression was identified in mature neurons. Thus N-twist overexpression does not inhibit neurogenesis, and may actually promote neurogenesis.
Faculty Mentor: Merritt Taylor, Biomedical Sciences
Sarala presented at the American Society of Cell Biology's 49th Annual Meeting, December 5-9,2009 in San Diego, CA.
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