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Foxp1 controls neural stem cell competence and bias towards deep layer cortical fates

Caroline Alayne Pearson, Destaye M. Moore, Haley O. Tucker, Joseph D. Dekker, Hui Hu, Amaya Miquelajáuregui, Bennett G. Novitch
doi: https://doi.org/10.1101/386276
Caroline Alayne Pearson
1department of Neurobiology, David Geffen School of Medicine at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
2Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
3Intellectual and Developmental Disabilities Research Center David Geffen School of Medicine at UCLA Los Angeles, CA 90095, USA
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Destaye M. Moore
1department of Neurobiology, David Geffen School of Medicine at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
2Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
3Intellectual and Developmental Disabilities Research Center David Geffen School of Medicine at UCLA Los Angeles, CA 90095, USA
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Haley O. Tucker
4Molecular Biosciences University of Texas at Austin Austin, Texas 78712
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Joseph D. Dekker
4Molecular Biosciences University of Texas at Austin Austin, Texas 78712
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Hui Hu
5Department of Microbiology School of Medicine University of Alabama at Birmingham Birmingham, AL 35205
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Amaya Miquelajáuregui
6Institute of Neurobiology University of Puerto Rico Medical Sciences Campus San Juan 00911, Puerto Rico
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Bennett G. Novitch
1department of Neurobiology, David Geffen School of Medicine at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
2Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
3Intellectual and Developmental Disabilities Research Center David Geffen School of Medicine at UCLA Los Angeles, CA 90095, USA
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  • For correspondence: bnovitch@ucla.edu
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Abstract

SUMMARY The laminar architecture of the mammalian neocortex depends on the orderly generation of distinct neuronal subtypes by apical radial glia (aRG) during embryogenesis. We identify critical roles for Foxp1 in maintaining RG identity and gating the temporal competency for early neurogenesis. High levels of Foxp1 are associated with early aRG and are required to promote proliferation and influence cell division symmetry, favoring aRG expansion and production of early born neurons. The potent pro-progenitor functions of Foxp1 are revealed through its ability to preserve a population of cells with aRG identity throughout development and extend the early neurogenic period into postnatal life. Foxp1 further promotes the formation of cells resembling basal RG (bRG), a progenitor group implicated in the increased size and complexity of the human cortex. Consistent with this role, we show that FOXP1 is associated with the initial formation and expansion of bRG during human corticogenesis.

HIGHLIGHTS

  • Foxp1 is transiently expressed by aRG during the early phase of corticogenesis

  • Foxp1 promotes self-renewing vertical cell divisions and aRG maintenance

  • Foxp1 gates the time window of deep layer neurogenesis

  • Ectopic Foxp1 expression can elicit bRG formation

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 07, 2018.
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Foxp1 controls neural stem cell competence and bias towards deep layer cortical fates
Caroline Alayne Pearson, Destaye M. Moore, Haley O. Tucker, Joseph D. Dekker, Hui Hu, Amaya Miquelajáuregui, Bennett G. Novitch
bioRxiv 386276; doi: https://doi.org/10.1101/386276
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Foxp1 controls neural stem cell competence and bias towards deep layer cortical fates
Caroline Alayne Pearson, Destaye M. Moore, Haley O. Tucker, Joseph D. Dekker, Hui Hu, Amaya Miquelajáuregui, Bennett G. Novitch
bioRxiv 386276; doi: https://doi.org/10.1101/386276

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