Abstract
Spinal cord patterning is orchestrated by multiple cell signalling pathways. Neural progenitors are maintained by Notch signalling, whereas ventral neural fates are specified by Hedgehog (Hh) signalling. However, how dynamic interactions between Notch and Hh signalling drive the precise pattern formation is still unknown. We applied the PHRESH (PHotoconvertible REporter of Signalling History) technique to analyse cell signalling dynamics in vivo during zebrafish spinal cord development. This approach reveals that Notch and Hh signalling display similar spatiotemporal kinetics throughout spinal cord patterning. Notch signalling functions upstream to control Hh response of neural progenitor cells. Using gain- and loss-of-function tools, we demonstrate that this regulation occurs not at the level of upstream regulators or primary cilia, but rather at the level of Gli transcription factors. Our results indicate that Notch signalling maintains Hh responsiveness of neural progenitors via a Gli-dependent mechanism in the spinal cord.
Highlights
Patterning of the spinal cord relies on the action of multiple cell signalling pathways with precise spatial and temporal dynamics (Briscoe and Novitch, 2008)
Neural progenitors in the spinal cord are organised into discrete dorsoventral (DV) domains that can be identified by the combinatorial expression of conserved transcription factors (Alaynick et al, 2011; Dessaud et al, 2008; Jessell, 2000)
Spinal cord patterning is a dynamic process with complex interactions of cell signalling pathways in both space and time
Summary
Patterning of the spinal cord relies on the action of multiple cell signalling pathways with precise spatial and temporal dynamics (Briscoe and Novitch, 2008). The developing spinal cord employs anti-parallel signalling gradients of Bone Morphogenic Protein (BMP) and Hedgehog (Hh) to specify dorsal and ventral cell fates, respectively (Le Dreau and Martı, 2012). Cells acquire their fates via sensing both graded inputs. When Shh binds to Ptc, Smo inhibition is released, allowing Smo to translocate to the primary cilia (Corbit et al, 2005; Rohatgi et al, 2007) This leads to the activation of the Gli family of transcription factors, resulting in expression of downstream target genes
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