RT Journal Article
SR Electronic
T1 Cdx4 regulates the onset of spinal cord neurogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 177469
DO 10.1101/177469
A1 Piyush Joshi
A1 Andrew J. Darr
A1 Isaac Skromne
YR 2017
UL http://biorxiv.org/content/early/2017/08/23/177469.abstract
AB The transition of cells from one developmental state to the next is driven by signaling cues interpreted by intracellular networks of transcription factors. In the vertebrate spinal cord, the progressive caudal-to-rostral maturation of cells is controlled by the signaling activities of FGF/Wnt antagonizing Retinoic Acid (RA): FGF/Wnt secreted from the caudal stem zone promote stem cell identities, whereas RA secreted from the somites promotes neural differentiation. It is unclear how intracellular transcription factor networks interpret these extracellular signaling cues. Using transient gene manipulation techniques in chicken, we show that Cdx4 is at the core of the transcription factor network that integrates upstream signaling information to regulate the sequential maturation of spinal cord neural progenitor cells. We show that Cdx4 represses the stem cell marker Sax1 and promotes expression of the neural identity gene Pax6 while simultaneously preventing the activation of the Pax6-dependent, neural-differentiation gene Ngn2. Our results suggest a novel role for Cdx4 in regulating the sequential maturation of neural cell states during early spinal cord development. Given Cdx factors established role in the transcriptional regulation of Hox patterning genes, we propose that Cdx factors coordinate the axial specification and maturation of cells during spinal cord development.