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Integrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genes
Craniofacial disorders are among the most common congenital defects. Here, the authors examined the genetic causes of non-syndromic craniofacial disorders during human development through analysis of gene expression and epigenomics.
- Tara N. Yankee
- , Sungryong Oh
- & Justin Cotney
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Opposing gene regulatory programs governing myofiber development and maturation revealed at single nucleus resolution
Researchers used single-nucleus RNA and ATAC sequencing to create an atlas of skeletal muscle development. They identified the gene programs and transcription factors that control muscle fiber development and maturation.
- Matthieu Dos Santos
- , Akansha M. Shah
- & Eric N. Olson
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Hedgehog signaling via its ligand DHH acts as cell fate determinant during skeletal muscle regeneration
Successful skeletal muscle regeneration relies on the interplay of multiple cell populations. Here, the authors describe how ciliary Hedgehog signaling coordinates the intercellular crosstalk required to balance wound healing and fatty fibrosis.
- Alessandra M. Norris
- , Ambili Bai Appu
- & Daniel Kopinke
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M1BP is an essential transcriptional activator of oxidative metabolism during Drosophila development
The transcriptional regulation of mitochondrial oxidative phosphorylation gene expression is poorly understood. Using the developing Drosophila flight muscle, the authors identify the transcription factor M1BP as a new major regulator of this process.
- Gabriela Poliacikova
- , Marine Barthez
- & Andrew J. Saurin
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A single-cell transcriptional atlas reveals resident progenitor cell niche functions in TMJ disc development and injury
The transcriptional network in TMJ disc development and injury remains poorly characterized. Here they generate a scRNA-seq atlas of mouse TMJ disc, and identify the resident progenitor population and how its transcriptional reprogramming contributes to disc repair.
- Ruiye Bi
- , Qing Yin
- & Songsong Zhu
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Adipose tissue is a source of regenerative cells that augment the repair of skeletal muscle after injury
The dynamics of fibroadipogenic progenitors (FAPs) after muscle injury are crucial to ensure efficient regeneration. Here the authors show that a pool of FAPs originates from adipose tissue and are necessary for effective muscle regeneration.
- Quentin Sastourné-Arrey
- , Maxime Mathieu
- & Coralie Sengenès
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Identification of evolutionarily conserved regulators of muscle mitochondrial network organization
Mitochondrial networks are carefully positioned to facilitate energy distribution within muscle cells. Here they show that energetic demands and conserved transcription factors regulate mitochondrial network organization and contractile phenotypes independently in Drosophila.
- Prasanna Katti
- , Peter T. Ajayi
- & Brian Glancy
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Mitochondrial network configuration influences sarcomere and myosin filament structure in striated muscles
How different physical configurations between sarcomeres and mitochondria alter energetic support for contractile function of skeletal muscle is not clear. Here the authors use advanced 3D imaging and analysis techniques to show how space is made for mitochondria within the tightly packed sarcomere networks of striated muscle cells.
- Prasanna Katti
- , Alexander S. Hall
- & Brian Glancy
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MRTF specifies a muscle-like contractile module in Porifera
Myocytes are a key cell type that enable animal movement, but their evolutionary origins remain unclear. Colgren and Nichols describe molecular and functional similarities between a contractile module in tissues of a sponge and muscle tissues in other animals, indicating a common evolutionary origin.
- J. Colgren
- & S. A. Nichols
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Control of CRK-RAC1 activity by the miR-1/206/133 miRNA family is essential for neuromuscular junction function
The miR-1/133/206 gene family codes for the most abundant microRNAs in striated muscles. Here, Klockner et al show that inactivation of all family members in skeletal muscle prevents formation of normal neuromuscular junctions due to increased expression of the adaptor protein CRK.
- Ina Klockner
- , Christian Schutt
- & Thomas Braun
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Spatiotemporal expression of regulatory kinases directs the transition from mitosis to cellular morphogenesis in Drosophila
The mechanisms regulating mitosis and differentiation during development are thought to be distinct. Here they show that in Drosophila the mitotic kinase Polo regulates cellular morphogenesis after cell cycle exit.
- Shuo Yang
- , Jennifer McAdow
- & Aaron N. Johnson
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Unexpected contribution of fibroblasts to muscle lineage as a mechanism for limb muscle patterning
The dogma is that limb muscle cells originate from somite, while connective tissue fibroblasts derive from lateral plate mesoderm. Here the authors identify a fibroblast population that undergoes myoblast conversion in response to BMP and contributes nuclei to myotubes at the myotendinous junction.
- Joana Esteves de Lima
- , Cédrine Blavet
- & Delphine Duprez
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Myofibril and mitochondria morphogenesis are coordinated by a mechanical feedback mechanism in muscle
Mitochondria produce high amounts of ATP to power myosin motors and sustained muscle contraction. Here, the authors show that during development, muscles coordinate the morphogenesis of their myofibrils directly with their mitochondria to optimize both for the physiological needs of each muscle-type.
- Jerome Avellaneda
- , Clement Rodier
- & Frank Schnorrer
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TGFβ signalling acts as a molecular brake of myoblast fusion
Fusion of myoblasts is essential for muscle development and repair, but the molecular mechanism underlying this process remains unclear. Here, the authors show, using chicken embryos as a model, that TGFβ signalling inhibits fusion via a receptor complementation mechanism, and indicate the involvement of endocytic degradation of activated receptors in modulation of this process.
- Julie Melendez
- , Daniel Sieiro
- & Christophe Marcelle
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TGFβ signaling curbs cell fusion and muscle regeneration
The fusion of muscle progenitor cells to form syncytial myofibers is required for skeletal muscle development and regeneration. Here, the authors describe a novel and specific molecular regulation of muscle cell fusion driven by transforming growth factor beta (TGFβ) signaling.
- Francesco Girardi
- , Anissa Taleb
- & Fabien Le Grand
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Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers
Mammalian skeletal muscle is composed of multinucleated myofibers, containing hundreds of nuclei that coordinate cellular function. Here, the authors show that single-nucleus RNA-sequencing reveals rare and emergent myonuclear populations, and uncovers dynamic transcriptional heterogeneity in development and aging.
- Michael J. Petrany
- , Casey O. Swoboda
- & Douglas P. Millay
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Single-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells
The transcriptional programs of nuclei in the muscle syncytium were assumed to be homogenous except at the neuromuscular and myotendinous junctions. Here, using single-nucleus transcriptomics, the authors reveal a previously unrecognized diversity and dynamics of myonuclear transcriptional programs.
- Minchul Kim
- , Vedran Franke
- & Carmen Birchmeier
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Small molecule screen in embryonic zebrafish using modular variations to target segmentation
Chemical screens can identify small molecules that affect biological development, with potential therapeutic value. Here, the authors use a modular approach in a screen in zebrafish embryos, varying concentration, genotype and timing to target segmentation disorders, birth defects that affect the spinal column.
- Sandra Richter
- , Ulrike Schulze
- & Andrew C. Oates
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Odd skipped-related 1 identifies a population of embryonic fibro-adipogenic progenitors regulating myogenesis during limb development
Fibro-adipogenic progenitors (FAPs) form part of interstitial muscle connective tissue (MCT) in adults but the origin of this non-myogenic lineage is unclear. Here, the authors show that Odd skipped related 1 (Osr1) in mice marks embryonic MCT, giving rise to FAPs, and loss of Osr1 in the limb causes muscle defects.
- Pedro Vallecillo-García
- , Mickael Orgeur
- & Sigmar Stricker
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The microprotein Minion controls cell fusion and muscle formation
Cellular fusion is essential for skeletal muscle development. Here the authors identify Minion as a microprotein required for myoblast fusion and skeletal muscle formation, and show that co-expression of Minion and Myomaker is sufficient to induce cytoskeletal rearrangement and cell fusion even in non-muscle cells.
- Qiao Zhang
- , Ajay A. Vashisht
- & Srihari C. Sampath
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Myomerger induces fusion of non-fusogenic cells and is required for skeletal muscle development
Cellular fusion is fundamental for skeletal muscle development. Here the authors show that myomerger is expressed in myoblasts, is essential for myoblast fusion in mice, and in co-operation with myomaker confers fusogenic ability to non-fusogenic cells.
- Malgorzata E. Quinn
- , Qingnian Goh
- & Douglas P. Millay
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Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells
Pericytes and vascular smooth muscle cells are crucial for functional blood vessels, but the developmental sources of these cells are incompletely understood. Here, the authors show that endocardial endothelial cells give rise to cardiac mural cells, which are controlled by Wnt signalling.
- Qi Chen
- , Hui Zhang
- & Ralf H. Adams
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Laminin regulates PDGFRβ+ cell stemness and muscle development
Muscle PDGFRβ+ cells are interstitial stem/progenitor cells with myogenic potential. Here, Yao et al. show that PDGFRβ+cell-derived laminin actively regulates their proliferation, differentiation and fate determination.
- Yao Yao
- , Erin H. Norris
- & Sidney Strickland
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Stabilin-2 modulates the efficiency of myoblast fusion during myogenic differentiation and muscle regeneration
Phosphatidylserine and its receptors are associated with cell-cell fusion. Here, the authors show the phosphatidylserine receptor stabilin-2 is expressed by muscle cells and plays a vital role in myoblast fusion and post-injury muscle regeneration in mice.
- Seung-Yoon Park
- , Youngeun Yun
- & In-San Kim
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E2F function in muscle growth is necessary and sufficient for viability in Drosophila
The transcriptional regulators E2F/Dp play a critical role in cell-cycle regulation, but it is unclear why E2F-deficient flies die. Here, the authors show this is linked to the function of E2F in adult Drosophilaskeletal muscle, with the contribution of E2f1 being most important in post-fusion muscle.
- Maria Paula Zappia
- & Maxim V. Frolov
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Linc-YY1 promotes myogenic differentiation and muscle regeneration through an interaction with the transcription factor YY1
Long intervening noncoding RNAs (lincRNAs) are an emerging class of molecular regulators with diverse functions. Here the authors identify Linc-YY1, a novel lincRNA transcribed from the noncoding region of the mouse YY1 gene, that binds to YY1 protein and thereby regulates skeletal muscle differentiation and regeneration.
- Liang Zhou
- , Kun Sun
- & Huating Wang
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CX3CR1 deficiency promotes muscle repair and regeneration by enhancing macrophage ApoE production
Chemokine-driven infiltration of inflammatory macrophages is central to the muscle regenerative response to injury. Here the authors show that the function of infiltrating macrophages is also important as notexin-induced muscle injury in mice is rescued by CX3CR1 knockout owing to enhanced ApoE production.
- Ludovic Arnold
- , Hélène Perrin
- & Christophe Combadiere
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Turning terminally differentiated skeletal muscle cells into regenerative progenitors
Newts can regenerate amputated limbs via unknown mechanism involving dedifferentiation of cells in the stump into progenitors that contribute to the new appendages. Here the authors show that skeletal muscle dedifferentiation in regenerating newt limbs relies on a diverted programmed cell death response by myofibers.
- Heng Wang
- , Sara Lööf
- & András Simon
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MicroRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice
Skeletal muscle stem cells (satellite cells) express different levels of a critical transcriptional regulator Pax7. Here, the authors show that miR-431 regulates Pax7 levels in satellite cells of the developing and regenerating muscle, and that increased miR-431expression in these cells alleviates symptoms of muscular dystrophy in mice.
- Rimao Wu
- , Hu Li
- & Dahai Zhu
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The transcription factor Foxc1 is necessary for Ihh–Gli2-regulated endochondral ossification
Skeletal development relies on endochondral ossification. Here the authors show that transcription factors Foxc1 and Gli2 interact to modulate expression of Ihh target genes that control endochondral ossification, and that disruption of this interaction partly underlies skeletal disorders in the Axenfeld–Rieger syndrome.
- Michiko Yoshida
- , Kenji Hata
- & Toshiyuki Yoneda
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The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre size
The Yes-associated protein (YAP) is a core effector of the Hippo pathway, which regulates proliferation and apoptosis in organ development, but its function in adult skeletal muscle remains poorly defined. Here the authors show that YAP is an essential regulator of myofibre size in adult skeletal muscle, via interaction with TEAD transcription factors.
- K. I. Watt
- , B. J. Turner
- & P. Gregorevic
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Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes
The transcription factor Sox9 together with its co-regulators promotes chondrocyte differentiation. Here Hata et al.find that Arid5b acts as a transcriptional co-regulator of Sox9 by regulating histone demethylation of Sox9 target genes during chondrogenesis in mice.
- Kenji Hata
- , Rikako Takashima
- & Toshiyuki Yoneda
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MG53-induced IRS-1 ubiquitination negatively regulates skeletal myogenesis and insulin signalling
The protein MG53 is known to inhibit myogenesis. Here, Ko et al. show that MG53 is an E3 ubiquitin ligase that mediates degradation of insulin receptor substrate 1 in skeletal muscle, thereby regulating myogenesis and insulin sensitivity in vitro and in vivo.
- Jae-Sung Yi
- , Jun Sub Park
- & Young-Gyu Ko
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The developmental basis of bat wing muscle
Phylogenetic bat studies suggest that powered flight is evolutionarily conserved. Tokita et al.find that bat wing muscles are derived from multiple myogenic sources with different embryonic origins, and that spatiotemporal correlations exist between outgrowth of wing membranes and expansion of wing muscles.
- Masayoshi Tokita
- , Takaaki Abe
- & Kazuo Suzuki
Single cell atlas of Xenoturbella bocki highlights limited cell-type complexity