Notch Signalling Maintains Hedgehog Responsiveness Via a Gli-dependent Mechanism During Spinal Cord Patterning in Zebrafish

Overview

Journal Elife

Specialty Biology

Date 2019 Aug 28

PMID 31453809

Citations 15

Authors

Craig T Jacobs

Peng Huang

Affiliations

Soon will be listed here.

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 (otoconvertible porter of ignalling istory) 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.

Citing Articles

Notch and Hedgehog Signaling Unveiled: Crosstalk, Roles, and Breakthroughs in Cancer Stem Cell Research.

Iluta S, Nistor M, Buruiana S, Dima D Life (Basel). 2025; 15(2).

PMID: 40003637 PMC: 11856057. DOI: 10.3390/life15020228.

Epigenetic priming of neural progenitors by Notch enhances Sonic hedgehog signaling and establishes gliogenic competence.

Tran L, Shinde A, Schuster K, Sabaawy A, Dale E, Welch M bioRxiv. 2025; .

PMID: 39896669 PMC: 11785114. DOI: 10.1101/2025.01.20.633996.

Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.

Huang X, Chen W, Wang Y, Shytikov D, Wang Y, Zhu W Front Med. 2025; 19(1):23-52.

PMID: 39745621 DOI: 10.1007/s11684-024-1107-1.

Toll-like receptors as a missing link in Notch signaling cascade during neurodevelopment.

Stojanovic M, Kalanj-Bognar S Front Mol Neurosci. 2024; 17:1465023.

PMID: 39664114 PMC: 11631889. DOI: 10.3389/fnmol.2024.1465023.

Targeting Notch signaling pathways with natural bioactive compounds: a promising approach against cancer.

Yang J, Sun Q, Liu X, Yang Y, Rong R, Yan P Front Pharmacol. 2024; 15:1412669.

PMID: 39092224 PMC: 11291470. DOI: 10.3389/fphar.2024.1412669.

References

Glazer A, Wilkinson A, Backer C, Lapan S, Gutzman J, Cheeseman I . The Zn finger protein Iguana impacts Hedgehog signaling by promoting ciliogenesis. Dev Biol. 2009; 337(1):148-56. PMC: 2799895. DOI: 10.1016/j.ydbio.2009.10.025. View

Scheer N, Campos-Ortega J . Use of the Gal4-UAS technique for targeted gene expression in the zebrafish. Mech Dev. 1999; 80(2):153-8. DOI: 10.1016/s0925-4773(98)00209-3. View

Bai C, Joyner A . Gli1 can rescue the in vivo function of Gli2. Development. 2001; 128(24):5161-72. DOI: 10.1242/dev.128.24.5161. View

Kageyama R, Ohtsuka T, Shimojo H, Imayoshi I . Dynamic Notch signaling in neural progenitor cells and a revised view of lateral inhibition. Nat Neurosci. 2008; 11(11):1247-51. DOI: 10.1038/nn.2208. View

Bae Y, Shimizu T, Hibi M . Patterning of proneuronal and inter-proneuronal domains by hairy- and enhancer of split-related genes in zebrafish neuroectoderm. Development. 2005; 132(6):1375-85. DOI: 10.1242/dev.01710. View

Tay S, Yu X, Wong K, Panse P, Peng Ng C, Roy S . The iguana/DZIP1 protein is a novel component of the ciliogenic pathway essential for axonemal biogenesis. Dev Dyn. 2009; 239(2):527-34. DOI: 10.1002/dvdy.22199. View

Ericson J, Morton S, Kawakami A, Roelink H, Jessell T . Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity. Cell. 1996; 87(4):661-73. DOI: 10.1016/s0092-8674(00)81386-0. View

Huang P, Xiong F, Megason S, Schier A . Attenuation of Notch and Hedgehog signaling is required for fate specification in the spinal cord. PLoS Genet. 2012; 8(6):e1002762. PMC: 3369957. DOI: 10.1371/journal.pgen.1002762. View

Ringuette R, Atkins M, Lagali P, Bassett E, Campbell C, Mazerolle C . A Notch-Gli2 axis sustains Hedgehog responsiveness of neural progenitors and Müller glia. Dev Biol. 2016; 411(1):85-100. DOI: 10.1016/j.ydbio.2016.01.006. View

10.

Briscoe J, Therond P . The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol. 2013; 14(7):416-29. DOI: 10.1038/nrm3598. View

11.

Bussmann J, Schulte-Merker S . Rapid BAC selection for tol2-mediated transgenesis in zebrafish. Development. 2011; 138(19):4327-32. DOI: 10.1242/dev.068080. View

12.

Eggenschwiler J, Anderson K . Cilia and developmental signaling. Annu Rev Cell Dev Biol. 2007; 23:345-73. PMC: 2094042. DOI: 10.1146/annurev.cellbio.23.090506.123249. View

13.

Wang X, Zhao Z, Muller J, Iyu A, Khng A, Guccione E . Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish. Biol Open. 2013; 2(11):1203-13. PMC: 3828767. DOI: 10.1242/bio.20136262. View

14.

Dessaud E, Ribes V, Balaskas N, Yang L, Pierani A, Kicheva A . Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen sonic hedgehog. PLoS Biol. 2010; 8(6):e1000382. PMC: 2879390. DOI: 10.1371/journal.pbio.1000382. View

15.

Li Y, Hibbs M, Gard A, Shylo N, Yun K . Genome-wide analysis of N1ICD/RBPJ targets in vivo reveals direct transcriptional regulation of Wnt, SHH, and hippo pathway effectors by Notch1. Stem Cells. 2012; 30(4):741-52. PMC: 3734558. DOI: 10.1002/stem.1030. View

16.

Briscoe J, Small S . Morphogen rules: design principles of gradient-mediated embryo patterning. Development. 2015; 142(23):3996-4009. PMC: 4712844. DOI: 10.1242/dev.129452. View

17.

Tyurina O, Guner B, Popova E, Feng J, Schier A, Kohtz J . Zebrafish Gli3 functions as both an activator and a repressor in Hedgehog signaling. Dev Biol. 2004; 277(2):537-56. DOI: 10.1016/j.ydbio.2004.10.003. View

18.

Wolff C, Roy S, Lewis K, Schauerte H, Joerg-Rauch G, Kirn A . iguana encodes a novel zinc-finger protein with coiled-coil domains essential for Hedgehog signal transduction in the zebrafish embryo. Genes Dev. 2004; 18(13):1565-76. PMC: 443519. DOI: 10.1101/gad.296004. View

19.

Artavanis-Tsakonas S, Simpson P . Choosing a cell fate: a view from the Notch locus. Trends Genet. 1991; 7(11-12):403-8. DOI: 10.1016/0168-9525(91)90264-q. View

20.

Itoh M, Kim C, Palardy G, Oda T, Jiang Y, Maust D . Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. Dev Cell. 2003; 4(1):67-82. DOI: 10.1016/s1534-5807(02)00409-4. View