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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.
Abstract:
The progression of cells down different lineage pathways is a collaborative effort 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.
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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