Notch signalling maintains Hedgehog responsiveness via a Gli-dependent mechanism during spinal cord patterning in zebrafish

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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.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

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Craig T Jacobs

Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0459-2838
Peng Huang

Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada

For correspondence
huangp@ucalgary.ca

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7954-8869

Funding

Natural Sciences and Engineering Research Council of Canada (RGPIN-2015-06343)

Peng Huang

Canada Foundation for Innovation (Project 32920)

Peng Huang

Alberta Children's Hospital Research Institute (Startup fund)

Peng Huang

Alberta Children's Hospital Research Institute (Graduate Scholarship)

Craig T Jacobs

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures was conducted in accordance with the principles outlined in the current Guidelines of the Canadian Council on Animal Care. All protocols were approved by the Animal Care Committee at the University of Calgary (#AC17-0128).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.