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FoxD5 domains and their effects on Neural Fate Stabilization Genes. Open Access

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Stem cell therapy is expected to greatly benefit the treatment of neurodegenerative diseases. In order to generate ideal transplantable Neural Stem Cells (NSCs) we need neurally committed stem cells that have not yet initiated a differentiation program. The FoxD5 gene is known to act at an upstream position to 11 other Neural Fate Stabilization (NFS) genes to maintain an undifferentiated neural ectoderm in the embryo during the early steps of neural plate formation. To understand how this gene transcriptionally regulates the NFS genes, I made several mutant versions of the FoxD5 proteins and tested their ability to repress or ectopically induce gene expression. An acidic blob domain in the N terminus is required for activation of gem, sox11 and zic2 , and a small region in the C-terminus, which contains an EH-1 domain, is required for repression. Defining the functional domains of the FoxD5 protein will allow us to understand how it regulates the NFS genes to curtail differentiation of neurally committed stem cells and maintain them in an immature state.

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