title: Shaping leg muscles in Drosophila: role of ladybird, a conserved regulator of appendicular myogenesis.
abstract: Legs are locomotor appendages used by a variety of evolutionarily distant vertebrates and invertebrates. The primary biological leg function, locomotion, requires the formation of a specialised appendicular musculature. Here we report evidence that ladybird, an orthologue of the Lbx1 gene recognised as a hallmark of appendicular myogenesis in vertebrates, is expressed in leg myoblasts, and regulates the shape, ultrastructure and functional properties of leg muscles in Drosophila. Ladybird expression is progressively activated in myoblasts associated with the imaginal leg disc and precedes that of the founder cell marker dumbfounded. The RNAi-mediated attenuation of ladybird expression alters properties of developing myotubes, impairing their ability to grow and interact with the internal tendons and epithelial attachment sites. It also affects sarcomeric ultrastructure, resulting in reduced leg muscle performance and impaired mobility in surviving flies. The over-expression of ladybird also results in an abnormal pattern of dorsally located leg muscles, indicating different requirements for ladybird in dorsal versus ventral muscles. This differential effect is consistent with the higher level of Ladybird in ventrally located myoblasts and with positive ladybird regulation by extrinsic Wingless signalling from the ventral epithelium. In addition, ladybird expression correlates with that of FGF receptor Heartless and the read-out of FGF signalling downstream of FGF. FGF signals regulate the number of leg disc associated myoblasts and are able to accelerate myogenic differentiation by activating ladybird, leading to ectopic muscle fibre formation. A key role for ladybird in leg myogenesis is further supported by its capacity to repress vestigial and to down-regulate the vestigial-governed flight muscle developmental programme. Thus in Drosophila like in vertebrates, appendicular muscles develop from a specialised pool of myoblasts expressing ladybird/Lbx1. The ladybird/Lbx1 gene family appears as a part of an ancient genetic circuitry determining leg-specific properties of myoblasts and making an appendage adapted for locomotion.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U384, Faculté de Medecine, Clermont-Ferrand, France.
authors.forename: Tariq
authors.initials: T
authors.lastname: Maqbool
authors.forename: Cedric
authors.initials: C
authors.lastname: Soler
authors.forename: Teresa
authors.initials: T
authors.lastname: Jagla
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Daczewska
authors.forename: Neha
authors.initials: N
authors.lastname: Lodha
authors.forename: Sudhir
authors.initials: S
authors.lastname: Palliyil
authors.forename: K
authors.initials: K
authors.lastname: VijayRaghavan
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jagla
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005075:Biological Evolution; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development* / Q000502:physiology; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005121:Extremities / Q000254:growth & development; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D008124:Locomotion; D008297:Male; D024510:Muscle Development / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000254:growth & development; D032448:Myoblasts, Skeletal / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C086967:Lbe protein, Drosophila; D014157:Transcription Factors; D051155:Wnt1 Protein; C103969:lbl protein, Drosophila; C074622:wg protein, Drosophila; D005346:Fibroblast Growth Factors