CDX4 regulates the progression of neural maturation in the spinal cord

Piyush Joshi1, Andrew J Darr2, Isaac Skromne3

  • 1Department of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, Florida, 33146, United States; Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, 600 5th St S, St. Petersburg, FL 33701, United States.

Developmental Biology
|March 3, 2019
PubMed

Insights

CDX4 is a key transcription factor in the developing spinal cord. It controls neural progenitor maturation by repressing early differentiation markers and promoting later ones, coordinating axial specification.

Area of Science:

  • Developmental biology
  • Neuroscience
  • Genetics

Background:

  • Cell lineage progression involves extracellular signals and intracellular transcription factors.
  • Vertebrate spinal cord development relies on FGF, Wnt, and Retinoic Acid signaling pathways.
  • The gene regulatory network controlling neural progenitor maturation is not fully understood.

Purpose of the Study:

  • To map the gene regulatory network controlling neural progenitor maturation in the chicken pre-neural tube.
  • To identify key transcription factors involved in this process.
  • To elucidate the function of CDX4 in regulating cell potency and differentiation.

Main Methods:

  • Gene regulatory network mapping in the chicken pre-neural tube.
  • Analysis of transcription factor function, including CDX4.
  • Investigating the roles of Nkx1.2, Pax6, and Ngn2 in neural differentiation.
  • Examining the influence of Retinoic Acid signaling.

Main Results:

  • CDX4 was identified as a dual-function core component regulating cell potency and differentiation.
  • CDX4 represses the early marker Nkx1.2 and promotes the late marker Pax6 in a caudal-to-rostral direction.
  • CDX4 prevents premature PAX6-dependent neural differentiation by inhibiting Ngn2 activation.
  • Retinoic Acid signaling restricts CDX4's regulation of Pax6 to the rostral pre-neural tube.

Conclusions:

  • CDX4 is integral to the gene regulatory network governing sequential neural progenitor maturation in the spinal cord.
  • CDX4 coordinates the transition from high to low potency during neural progenitor development.
  • CDX factors likely coordinate spinal cord maturation and axial specification, building on their known role in Hox gene regulation.

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