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Fezf2 directs the differentiation of corticofugal neurons from striatal progenitors in vivo

Abstract

In the developing cerebral cortex, cell-extrinsic and cell-intrinsic signals govern the establishment of neuron subtype-specific identity. Here we show that, within the niche of the striatum, the expression of a single transcription factor, Fezf2, is sufficient to generate corticofugal neurons from progenitors fated to become medium spiny neurons. This demonstrates that a specific population of cortical projection neurons can be directed to differentiate outside of the cortex by cell-autonomous signaling.

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Figure 1: LGE progenitors generate neurons with corticofugal molecular properties in response to Fezf2.
Figure 2: Fezf2GFP-electroporated neurons do not express markers of MSN.
Figure 3: Fezf2 instructs the generation of CFu neurons from LGE progenitors without expression of cortical progenitor-specific genes.

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Acknowledgements

We thank J. Macklis (Harvard University) for reagents and advice; E. Abdel-Azim, G. Srubek-Tomassy, F. Zhang and S. Lodato for their comments; R. Hevner, (University of Washington), C. Lois (M.I.T.), K. Campbell (University of Cincinnati) and Q. Ma (Harvard Medical School) for generous sharing of antibodies, probes and expression vectors; and A. Meleski, A. Merlino and Z. Trayes-Gibson for technical support. This work was partially supported by grants to P.A. from the US National Institutes of Health (NS062849), the Spastic Paraplegia Foundation, the Harvard Stem Cell Institute and the Harvard NeuroDiscovery Center to P.A.; C.R. was partially supported by a Milton-Safenowitz postdoctoral fellowship from the ALS Association.

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P.A. and C.R. conceived the experiments and wrote the manuscript. P.A. supervised the project and C.R. executed all the experiments.

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Correspondence to Paola Arlotta.

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The authors declare no competing financial interests.

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Supplementary Figures 1–5 and Supplementary Methods (PDF 4606 kb)

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Rouaux, C., Arlotta, P. Fezf2 directs the differentiation of corticofugal neurons from striatal progenitors in vivo. Nat Neurosci 13, 1345–1347 (2010). https://doi.org/10.1038/nn.2658

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