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CDX4 regulates the progression of neural maturation in the spinal cord

View ORCID ProfilePiyush Joshi, Andrew J. Darr, Isaac Skromne
doi: https://doi.org/10.1101/177469
Piyush Joshi
1Department of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, Florida, 33146, United States
2Cancer and Blood Disorders Institute, Johns Hopkins All Children’s Hospital, 600 5th St S, St. Petersburg, FL 33701
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Andrew J. Darr
3Department of Health Sciences Education, University of Illinois College of Medicine, 1 Illini Drive, Peoria, IL 61605
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Isaac Skromne
1Department of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, Florida, 33146, United States
4Department of Biology, University of Richmond, 28 Westhampton Way B322, Richmond, Virginia, 23173, United States
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  • For correspondence: iskromne@richmond.edu
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ABSTRACT

The progressive maturation of cells down differentiation lineages is controlled by collaborative interactions between networks of extracellular signals and intracellular transcription factors. In the vertebrate spinal cord, FGF, Wnt and Retinoic Acid signaling pathways regulate the progressive caudal-to-rostral maturation of neural progenitors by regulating a poorly understood gene regulatory network of transcription factors. We have mapped out this gene regulatory network in the chicken pre-neural tube, identifying CDX4 as a dual-function core component that simultaneously regulates gradual loss of cell potency and acquisition of differentiation states: in a caudal-to-rostral direction, CDX4 represses the early neural differentiation marker Nkx1.2 and promotes the late neural differentiation marker Pax6. Significantly, CDX4 prevents premature PAX6-dependent neural differentiation by blocking Ngn2 activation. This regulation of CDX4 over Pax6 is restricted to the rostral pre-neural tube by Retinoic Acid signaling. Together, our results show that in the spinal cord, CDX4 is part of the gene regulatory network controlling the sequential and progressive transition of states from high to low potency during neural progenitor maturation. Given CDX well-known involvement in Hox gene regulation, we propose that CDX factors coordinate the maturation and axial specification of neural progenitor cells during spinal cord development.

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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-ND 4.0 International license.
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Posted December 26, 2018.
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CDX4 regulates the progression of neural maturation in the spinal cord
Piyush Joshi, Andrew J. Darr, Isaac Skromne
bioRxiv 177469; doi: https://doi.org/10.1101/177469
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CDX4 regulates the progression of neural maturation in the spinal cord
Piyush Joshi, Andrew J. Darr, Isaac Skromne
bioRxiv 177469; doi: https://doi.org/10.1101/177469

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