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Neural crest regulates myogenesis through the transient activation of NOTCH

Abstract

How dynamic signalling and extensive tissue rearrangements interact to generate complex patterns and shapes during embryogenesis is poorly understood1,2,3. Here we characterize the signalling events taking place during early morphogenesis of chick skeletal muscles. We show that muscle progenitors present in somites require the transient activation of NOTCH signalling to undergo terminal differentiation. The NOTCH ligand Delta1 is expressed in a mosaic pattern in neural crest cells that migrate past the somites. Gain and loss of Delta1 function in neural crest modifies NOTCH signalling in somites, which results in delayed or premature myogenesis. Our results indicate that the neural crest regulates early muscle formation by a unique mechanism that relies on the migration of Delta1-expressing neural crest cells to trigger the transient activation of NOTCH signalling in selected muscle progenitors. This dynamic signalling guarantees a balanced and progressive differentiation of the muscle progenitor pool.

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Figure 1: Notch is active during early myogenesis.
Figure 2: NOTCH signalling is necessary for myogenesis.
Figure 3: Myogenesis requires the transient activation of NOTCH.
Figure 4: Neural crest regulates myogenesis in somites through NOTCH signalling.

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Acknowledgements

We thank N. Rosenthal and P. Currie for critical reading of the manuscript. This study was funded by grants from the Agence Nationale pour le Recherche (ANR), and by the EU 6th Framework Programme Network of Excellence MYORES. The help of P. Weber, S. Firth, C. Johnson and I. Harper from Imaging Facilities (IBDML, Marseille and MMI, Monash University) is acknowledged.

Author information

Authors and Affiliations

Authors

Contributions

A.C.R. and C.M conceived the experiments. A.C.R. predominantly performed the work with the help of O.S. D.S. designed the animation. C.M. supervised the project and wrote the paper.

Corresponding author

Correspondence to Christophe Marcelle.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1-14 with legends. (PDF 3505 kb)

Supplementary Movie 1

This movie contains a time-lapse confocal analysis showing the rapid translocation of NOTCH-activating epithelial cells from the DML into the Transition Zone. The nuclei of the NOTCH-activating cells are in green, while all electroporated cells are in red. We estimated that it takes 90’ for a DML cell (such as the DML cell shown by a white dot) to activate NOTCH and translocate into the TZ. (ZIP 1807 kb)

Supplementary Movie 2

This movie contains a model describing the regulation of myogenesis by migrating, Delta1-expressing neural crest cells. As they migrate in close proximity to the medial border of the dermomyotome (DML, in green), Delta1-expressing neural crest establish physical contact with selected DML epithelial cells. The receiving cell transiently activates NOTCH signaling, initiates MYF5 expression (in yellow) and translocates into the Transition Zone (TZ). NOTCH signaling is repressed before TZ cells undergo terminal differentiation, elongating into myocytes and translocating into the myotome (in red). Animation created with the free open source 3D software Blender (www.blender.org). (ZIP 5988 kb)

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Rios, A., Serralbo, O., Salgado, D. et al. Neural crest regulates myogenesis through the transient activation of NOTCH. Nature 473, 532–535 (2011). https://doi.org/10.1038/nature09970

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