LanB1 Cooperates With Kon-Tiki During Embryonic Muscle Migration in Drosophila

Muscle development is a multistep process that involves cell specification, myoblast fusion, myotube migration, and attachment to the tendons. In spite of great efforts trying to understand the basis of these events, little is known about the molecular mechanisms underlying myotube migration. Knowledge of the few molecular cues that guide this migration comes mainly from studies in Drosophila. The migratory process of Drosophila embryonic muscles involves a first phase of migration, where muscle progenitors migrate relative to each other, and a second phase, where myotubes migrate searching for their future attachment sites. During this phase, myotubes form extensive filopodia at their ends oriented preferentially toward their attachment sites. This myotube migration and the subsequent muscle attachment establishment are regulated by cell adhesion receptors, such as the conserved proteoglycan Kon-tiki/Perdido. Laminins have been shown to regulate the migratory behavior of many cell populations, but their role in myotube migration remains largely unexplored. Here, we show that laminins, previously implicated in muscle attachment, are indeed required for muscle migration to tendon cells. Furthermore, we find that laminins genetically interact with kon-tiki/perdido to control both myotube migration and attachment. All together, our results uncover a new role for the interaction between laminins and Kon-tiki/Perdido during Drosophila myogenesis. The identification of new players and molecular interactions underlying myotube migration broadens our understanding of muscle development and disease.

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Epidermal tendon cells require Broad Complex function for correct attachment of the indirect flight muscles in Drosophila melanogaster

Journal of Cell Science ◽

10.1242/jcs.112.22.4051 ◽

1999 ◽

Vol 112 (22) ◽

pp. 4051-4065 ◽

Cited By ~ 2

Author(s):

D.J. Sandstrom ◽

L.L. Restifo

Keyword(s):

Complex Function ◽

Myotendinous Junction ◽

Wild Type ◽

Muscle Attachment ◽

Attachment Sites ◽

Tendon Cells ◽

Flight Muscles ◽

Broad Complex ◽

Developing Muscle ◽

Dorsal Epidermis

Drosophila Broad Complex, a primary response gene in the ecdysone cascade, encodes a family of zinc-finger transcription factors essential for metamorphosis. Broad Complex mutations of the rbp complementation group disrupt attachment of the dorsoventral indirect flight muscles during pupal development. We previously demonstrated that isoform BRC-Z1 mediates the muscle attachment function of rbp(+) and is expressed in both developing muscle fibers and their epidermal attachment sites. We now report two complementary studies to determine the cellular site and mode of action of rbp(+) during maturation of the myotendinous junctions of dorsoventral indirect flight muscles. First, genetic mosaics, produced using the paternal loss method, revealed that the muscle attachment phenotype is determined primarily by the genotype of the dorsal epidermis, with the muscle fiber and the ventral epidermis exerting little or no influence. When the dorsal epidermis was mutant, the vast majority of muscles detached or chose ectopic attachment sites, regardless of the muscle genotype. Conversely, wild-type dorsal epidermis could support attachment of mutant muscles. Second, ultrastructural analysis corroborated and extended these results, revealing defective and delayed differentiation of rbp mutant epidermal tendon cells in the dorsal attachment sites. Tendon cell processes, the stress-bearing links between the epidermis and muscle, were reduced in number and showed delayed appearance of microtubule bundles. In contrast, mutant muscle and ventral epidermis resembled the wild type. In conclusion, BRC-Z1 acts in the dorsal epidermis to ensure differentiation of the myotendinous junction. By analogy with the cell-cell interaction essential for embryonic muscle attachment, we propose that BRC-Z1 regulates one or more components of the epidermal response to a signal from the developing muscle.

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Indirect flight muscles in Drosophila melanogaster as a tractable model to study muscle development and disease

The International Journal of Developmental Biology ◽

10.1387/ijdb.190333un ◽

2020 ◽

Vol 64 (1-2-3) ◽

pp. 167-173

Author(s):

Saroj Jawkar ◽

Upendra Nongthomba

Keyword(s):

Drosophila Melanogaster ◽

Muscle Development ◽

Myoblast Fusion ◽

Successful Development ◽

Adult Muscle ◽

Attachment Sites ◽

Flight Muscles ◽

And Function

Myogenesis is a complex multifactorial process leading to the formation of the adult muscle. An amalgamation of autonomous processes including myoblast fusion and myofibrillogenesis, as well as non-autonomous processes, such as innervations from neurons and precise connections with attachment sites, are responsible for successful development and function of muscles. In this review, we describe the development of the indirect flight muscles (IFMs) in Drosophila melanogaster, and highlight the use of the IFMs as a model for studying muscle development and disease, based on recent studies on the development and function of IFMs.

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Identification of the crucial molecular events during the large-scale myoblast fusion in sheep

Physiological Genomics ◽

10.1152/physiolgenomics.00184.2013 ◽

2014 ◽

Vol 46 (12) ◽

pp. 429-440 ◽

Cited By ~ 4

Author(s):

Caihong Wei ◽

Li Li ◽

Hongwei Su ◽

Lingyang Xu ◽

Jian Lu ◽

...

Keyword(s):

Large Scale ◽

Molecular Mechanisms ◽

Muscle Development ◽

Target Genes ◽

Myogenic Differentiation ◽

Myoblast Fusion ◽

Myoblast Differentiation ◽

Pcr Analysis ◽

Fetal Sheep ◽

Fetal Muscle

It is well known that in sheep most myofibers are formed before birth; however, the crucial myogenic stage and the cellular and molecular mechanisms underpinning phenotypic variation of fetal muscle development remain to be ascertained. We used histological, microarray, and quantitative real-time PCR (qPCR) methods to examine the developmental characteristics of fetal muscle at 70, 85, 100, 120, and 135 days of gestation in sheep. We show that day 100 is an important checkpoint for change in muscle transcriptome and histomorphology in fetal sheep and that the period of 85–100 days is the vital developmental stage for large-scale myoblast fusion. Furthermore, we identified the cis-regulatory motifs for E2F1 or MEF2A in a list of decreasingly or increasingly expressed genes between 85 and 100 days, respectively. Further analysis demonstrated that the mRNA and phosphorylated protein levels of E2F1 and MEF2A significantly declined with myogenic progression in vivo and in vitro. qRT-PCR analysis indicated that PI3K and FST, as targets of E2F1, may be involved in myoblast differentiation and fusion and that downregulation of MEF2A contributes to transition of myofiber types by differential regulation of the target genes involved at the stage of 85–100 days. We clarify for the first time the timing of myofiber proliferation and development during gestation in sheep, which would be beneficial to meat sheep production. Our findings present a repertoire of gene expression in muscle during large-scale myoblast fusion at transcriptome-wide level, which contributes to elucidate the regulatory network of myogenic differentiation.

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Intrinsic control of muscle attachment sites matching

eLife ◽

10.7554/elife.57547 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Alexandre Carayon ◽

Laetitia Bataillé ◽

Gaëlle Lebreton ◽

Laurence Dubois ◽

Aurore Pelletier ◽

...

Keyword(s):

Live Imaging ◽

Muscle Attachment ◽

Regulatory Modules ◽

Transcriptional Reprogramming ◽

Attachment Sites ◽

Tendon Cells ◽

Evolutionarily Conserved ◽

Selection Of ◽

Muscle Attachment Sites

Myogenesis is an evolutionarily conserved process. Little known, however, is how the morphology of each muscle is determined, such that movements relying upon contraction of many muscles are both precise and coordinated. Each Drosophila larval muscle is a single multinucleated fibre whose morphology reflects expression of distinctive identity Transcription Factors (iTFs). By deleting transcription cis-regulatory modules of one iTF, Collier, we generated viable muscle identity mutants, allowing live imaging and locomotion assays. We show that both selection of muscle attachment sites and muscle/muscle matching is intrinsic to muscle identity and requires transcriptional reprogramming of syncytial nuclei. Live-imaging shows that the staggered muscle pattern involves attraction to tendon cells and heterotypic muscle-muscle adhesion. Unbalance leads to formation of branched muscles, and this correlates with locomotor behavior deficit. Thus, engineering Drosophila muscle identity mutants allows to investigate, in vivo, physiological and mechanical properties of abnormal muscles.

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The Fertilization Enigma: How Sperm and Egg Fuse

Annual Review of Cell and Developmental Biology ◽

10.1146/annurev-cellbio-120219-021751 ◽

2021 ◽

Vol 37 (1) ◽

Author(s):

Victoria E. Deneke ◽

Andrea Pauli

Keyword(s):

Viral Entry ◽

Molecular Mechanisms ◽

Muscle Development ◽

Annual Review ◽

Publication Date ◽

Open Questions ◽

Singular Event ◽

Multistep Process ◽

Mammalian Fertilization ◽

Emerging Themes

Fertilization is a multistep process that culminates in the fusion of sperm and egg, thus marking the beginning of a new organism in sexually reproducing species. Despite its importance for reproduction, the molecular mechanisms that regulate this singular event, particularly sperm–egg fusion, have remained mysterious for many decades. Here, we summarize our current molecular understanding of sperm–egg interaction, focusing mainly on mammalian fertilization. Given the fundamental importance of sperm–egg fusion yet the lack of knowledge of this process in vertebrates, we discuss hallmarks and emerging themes of cell fusion by drawing from well-studied examples such as viral entry, placenta formation, and muscle development. We conclude by identifying open questions and exciting avenues for future studies in gamete fusion. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Phospholipase D1 facilitates second-phase myoblast fusion and skeletal muscle regeneration

Molecular Biology of the Cell ◽

10.1091/mbc.e14-03-0802 ◽

2015 ◽

Vol 26 (3) ◽

pp. 506-517 ◽

Cited By ~ 12

Author(s):

Shuzhi Teng ◽

David Stegner ◽

Qin Chen ◽

Tsunaki Hongu ◽

Hiroshi Hasegawa ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Muscle Development ◽

Myoblast Fusion ◽

Skeletal Muscle Regeneration ◽

Fusion Pore ◽

Myoblast Differentiation ◽

Second Phase ◽

Genetic Ablation ◽

Phospholipase D1

Myoblast differentiation and fusion is a well-orchestrated multistep process that is essential for skeletal muscle development and regeneration. Phospholipase D1 (PLD1) has been implicated in the initiation of myoblast differentiation in vitro. However, whether PLD1 plays additional roles in myoblast fusion and exerts a function in myogenesis in vivo remains unknown. Here we show that PLD1 expression is up-regulated in myogenic cells during muscle regeneration after cardiotoxin injury and that genetic ablation of PLD1 results in delayed myofiber regeneration. Myoblasts derived from PLD1-null mice or treated with PLD1-specific inhibitor are unable to form mature myotubes, indicating defects in second-phase myoblast fusion. Concomitantly, the PLD1 product phosphatidic acid is transiently detected on the plasma membrane of differentiating myocytes, and its production is inhibited by PLD1 knockdown. Exogenous lysophosphatidylcholine, a key membrane lipid for fusion pore formation, partially rescues fusion defect resulting from PLD1 inhibition. Thus these studies demonstrate a role for PLD1 in myoblast fusion during myogenesis in which PLD1 facilitates the fusion of mononuclear myocytes with nascent myotubes.

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Scx-positive tendon cells are required for correct muscle patterning

10.1101/2021.01.03.424463 ◽

2021 ◽

Author(s):

Yudai Ono ◽

Tempei Sato ◽

Chisa Shukunami ◽

Hiroshi Asahara ◽

Masafumi Inui

Keyword(s):

Skeletal Muscles ◽

Essential Role ◽

Cell Lineage ◽

Attachment Site ◽

Muscle Bundle ◽

Muscle Attachment ◽

Attachment Sites ◽

Tendon Cells ◽

Muscle Attachment Sites

SummaryThe elaborate movement of the vertebrate body is supported by the precise connection of muscle, tendon and bone. Each of the >600 distinct skeletal muscles in the human body has unique attachment sites; however, the mechanism through which muscles are reproducibly attached to designated partner tendons during embryonic development is incompletely understood. We herein show that Screlaxis-positive tendon cells have an essential role in correct muscle attachment in mouse embryos. Specific ablation of Screlaxis-positive cells resulted in dislocation of muscle attachment sites and abnormal muscle bundle morphology. Step-by-step observation of myogenic cell lineage revealed that post-fusion myofibers, but not migrating myoblasts, require tendon cells for their morphology. Furthermore, muscles could change their attachment site, even after the formation of the insertion. Our study demonstrated an essential role of tendon cells in the reproducibility and plasticity of skeletal muscle patterning, in turn revealing a novel tissue-tissue interaction in musculoskeletal morphogenesis.Graphical abstract

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