Notch Signalling Is Required for the Formation of Structurally Stable Muscle Fibres in Zebrafish

Susana Pascoal,Jonathan D Leslie,Leonor Saúde,Joana Esteves De Lima,Simon M Hughes,Henry H Roehl

doi:10.1371/journal.pone.0068021

Susana Pascoal, Jonathan D Leslie + Show 4 more

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https://doi.org/10.1371/journal.pone.0068021

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Abstract

BackgroundAccurate regulation of Notch signalling is central for developmental processes in a variety of tissues, but its function in pectoral fin development in zebrafish is still unknown.Methodology/Principal FindingsHere we show that core elements necessary for a functional Notch pathway are expressed in developing pectoral fins in or near prospective muscle territories. Blocking Notch signalling at different levels of the pathway consistently leads to the formation of thin, wavy, fragmented and mechanically weak muscles fibres and loss of stress fibres in endoskeletal disc cells in pectoral fins. Although the structural muscle genes encoding Desmin and Vinculin are normally transcribed in Notch-disrupted pectoral fins, their proteins levels are severely reduced, suggesting that weak mechanical forces produced by the muscle fibres are unable to stabilize/localize these proteins. Moreover, in Notch signalling disrupted pectoral fins there is a decrease in the number of Pax7-positive cells indicative of a defect in myogenesis.Conclusions/SignificanceWe propose that by controlling the differentiation of myogenic progenitor cells, Notch signalling might secure the formation of structurally stable muscle fibres in the zebrafish pectoral fin.

Highlights

The development of many organs starts with the formation of a primordium at specific embryonic locations in response to combinatorial positional signals
Little or no expression of the Notch ligand jagged2, the Notch transmembrane receptors notch1a, notch2 and notch3 and the direct Notch targets her6, her7 and her13.2 was detected by whole mount in situ hybridization at the level of the pectoral fin buds
Lack of Desmin protein is not a consequence of lack of desmin mRNA transcription as detected by in situ hybridization in mibta52b mutants pectoral fins (Fig. 6B, D). These results suggest that desmin might not be the primary cause of the muscle phenotype in mibta52b mutants but unveil the possibility, amongst others, that forces generated by mechanically stable muscle fibres are essential to maintain appropriate Desmin protein levels

Summary

Introduction

The development of many organs starts with the formation of a primordium at specific embryonic locations in response to combinatorial positional signals. This is the case with the appendages. The genetic network that triggers and controls paired fin outgrowth seems to be similar to the developmental program of the tetrapod limb until larval stages. In amniote tetrapods, paired appendage outgrowth is controlled along the proximal-distal (PD), anterior-posterior (AP) and dorsalventral (DV) axes by three organizing centres. Accurate regulation of Notch signalling is central for developmental processes in a variety of tissues, but its function in pectoral fin development in zebrafish is still unknown

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