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Differentiation and Subtype Specification of Spinal Motor Neurons through a Program of Foxp1, Foxp2, and Foxp4 Gene Expression: Therapeutic ... Medicine in Spinal Nerve Injury and Disease
David Leon Rousso
Paperback. ProQuest, UMI Dissertation Publishing 2011-09-03.
ISBN 9781243527912
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Publisher description
In my dissertation, I identify three members of the Forkhead family of transcription factors, Foxp1, Foxp2, and Foxp4, as expressed through successive stages of motor neuron development. Foxp1 is expressed by a subset of differentiated motor neurons which innervate the limb muscles and autonomic ganglia, and through comprehensive gain- and loss-of-function analyses I demonstrate that Foxp1 is both necessary and sufficient to program motor neuron precursor cells to acquire either of these subtype identities when combined with the appropriate Hox cofactor (Rousso et al., 2008). I also demonstrate that Foxp1 regulates the expression of Reelin signaling components to orchestrate the myotopic organization of motor columns (Palmesino, Rousso et al., 2010). Finally, I show that the differential expression of Foxp2 and Foxp4 characterizes different states of progenitor cell adhesion within the neuroepithelial stem cell niche. Through gain- and loss-of-function studies in mouse and chick models, I show that Foxp2 and Foxp4 act sequentially to restrict progenitor proliferation and accelerate neurogenic cell division by modulating the expression of N-cadherin. Taken together, I show that Foxp1/2/4 proteins integrate multiple aspects of spinal cord development, including progenitor cell-cycle regulation and epithelial adhesion; as well as post-mitotic specification, axon guidance, and cell soma migration. These studies have significant implications for neural repair in the spinal cord using stem cell transplantation or endogenous regeneration strategies
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Differentiation and Subtype Specification of Spinal Motor Neurons through a Program of Foxp1, Foxp2, and Foxp4 Gene Expression: Therapeutic ... Medicine in Spinal Nerve Injury and Disease
Book reviews » Differentiation and Subtype Specification of Spinal Motor Neurons through a Program of Foxp1, Foxp2, and Foxp4 Gene Expression: Therapeutic ... Medicine in Spinal Nerve Injury and Disease
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