4.4 Article

CDX4 regulates the progression of neural maturation in the spinal cord

Journal

DEVELOPMENTAL BIOLOGY
Volume 449, Issue 2, Pages 132-142

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2019.02.014

Keywords

CDX; Neurogenesis; Spinal cord; Gene regulatory network

Funding

  1. Sigma XI GIAR
  2. University of Miami College of Art and Science
  3. University of Miami College of Arts and Sciences
  4. National Science Foundation [IOS-090449, IOS-1755386]

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The progression of cells down different lineage pathways is a collaborative effort between networks of extra cellular 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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