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Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS.

Neuron | April 29, 2012 |

Rousso, David L | Pearson, Caroline Alayne | Gaber, Zachary B | Miquelajauregui, Amaya | Li, Shanru | Portera-Cailliau, Carlos | Morrisey, Edward E | Novitch, Bennett G
Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.

Abstract

Neuroepithelial attachments at adherens junctions are essential for the self-renewal of neural stem and progenitor cells and the polarized organization ... . Together, these data reveal a Foxp-based transcriptional mechanism that regulates the integrity and cytoarchitecture of neuroepithelial progenitors.

Neuroepithelial attachments at adherens junctions are essential for the self-renewal of neural stem and progenitor cells and the polarized organization of the developing central nervous system. The balance between stem cell maintenance and differentiation depends on the precise assembly and disassembly of these adhesive contacts, but the gene regulatory mechanisms orchestrating this process are not known. Here, we demonstrate that two Forkhead transcription factors, Foxp2 and Foxp4, are progressively expressed upon neural differentiation in the spinal cord. Elevated expression of either Foxp represses the expression of a key component of adherens junctions, N-cadherin, and promotes the detachment of differentiating neurons from the neuroepithelium. Conversely, inactivation of Foxp2 and Foxp4 function in both chick and mouse results in a spectrum of neural tube defects associated with neuroepithelial disorganization and enhanced progenitor maintenance. Together, these data reveal a Foxp-based transcriptional mechanism that regulates the integrity and cytoarchitecture of neuroepithelial progenitors.

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Nihms-364802-f0001
Fig 1. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.
Nihms-364802-f0001
Fig 1. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.

Fig 1

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Fig 2. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.
Nihms-364802-f0002
Fig 2. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.

Fig 2

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Nihms-364802-f0003
Fig 3. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.
Nihms-364802-f0003
Fig 3. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.

Fig 3

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Nihms-364802-f0004
Fig 4. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.
Nihms-364802-f0004
Fig 4. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.

Fig 4

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Nihms-364802-f0005
Fig 5. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.
Nihms-364802-f0005
Fig 5. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.

Fig 5

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Nihms-364802-f0006
Fig 6. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.
Nihms-364802-f0006
Fig 6. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.

Fig 6

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Nihms-364802-f0007
Fig 7. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.
Nihms-364802-f0007
Fig 7. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.

Fig 7

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Fig 8. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.
Nihms-364802-f0008
Fig 8. Rousso, Pearson, et al. "Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS." Neuron 74.2 (2012): 314-30. Web.

Fig 8

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