ABSTRACT
The integration of extracellular signals by intracellular transcription factor networks is a critical determinant of cell fate decisions during embryonic development. In the vertebrate spinal cord, the progressive caudal-to-rostral maturation of neural progenitors (NPs) is controlled by the signaling activities of FGF/Wnt antagonizing retinoic acid. The incompleteness of transcriptional gene regulatory network (GRN) involved hinders proper understanding of early spinal cord development. Using transient gene manipulation technique in chicken, we show that Cdx4 is at the core of the GRN that integrates upstream signaling information to regulate the sequential maturation of NPs. We show that Cdx4 represses the pluripotency gene Sax1 and promotes expression of the neural gene Pax6 while simultaneously preventing the activation of the Pax6-dependent neurogenic gene Ngn2. Our results suggest a novel role for Cdx4 in regulating the sequential transition of neural cell states during early spinal cord development. We propose that Cdx factors broadly coordinate axial specification and maturation of NPs during spinal cord development.
SUMMARY STATEMENT Cdx4 is at the core of a gene regulatory network the coordinates the sequential transition of neural cell states during early spinal cord development, from pluripotency to early differentiation.