RESUMO
Striated muscle fibers are characterized by their tightly organized cytoplasm. Here, we show that the Drosophila melanogaster KASH proteins Klarsicht (Klar) and MSP-300 cooperate in promoting even myonuclear spacing by mediating a tight link between a newly discovered MSP-300 nuclear ring and a polarized network of astral microtubules (aMTs). In either klar or msp-300(ΔKASH), or in klar and msp-300 double heterozygous mutants, the MSP-300 nuclear ring and the aMTs retracted from the nuclear envelope, abrogating this even nuclear spacing. Anchoring of the myonuclei to the core acto-myosin fibrillar compartment was mediated exclusively by MSP-300. This protein was also essential for promoting even distribution of the mitochondria and ER within the muscle fiber. Larval locomotion is impaired in both msp-300 and klar mutants, and the klar mutants were rescued by muscle-specific expression of Klar. Thus, our results describe a novel mechanism of nuclear spacing in striated muscles controlled by the cooperative activity of MSP-300, Klar, and astral MTs, and demonstrate its physiological significance.
Assuntos
Proteínas de Drosophila/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Microtúbulos/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/fisiologia , Miofibrilas/metabolismo , Organelas/metabolismo , Organelas/fisiologia , Actomiosina/genética , Actomiosina/metabolismo , Animais , Núcleo Celular/genética , Núcleo Celular/metabolismo , Núcleo Celular/fisiologia , Conectina , Proteínas de Drosophila/genética , Drosophila melanogaster , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/fisiologia , Locomoção/genética , Locomoção/fisiologia , Proteínas de Membrana Transportadoras/genética , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Microtúbulos/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/fisiologia , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Mutação/genética , Miofibrilas/genética , Membrana Nuclear/genética , Membrana Nuclear/metabolismo , Membrana Nuclear/fisiologia , Organelas/genéticaRESUMO
In the vertebrate head, mesoderm cells fuse together to form a myofiber, which is attached to specific cranial neural crest (CNC)-derived skeletal elements in a highly coordinated manner. Although it has long been recognized that CNC plays a role in the formation of the head musculature, the precise molecular underpinnings of this process remain elusive. In the present study we explored the nature of the crosstalk between CNC and mesoderm cells during head muscle development, employing three models for genetic perturbations of CNC development in mice, as well as experimental ablation of CNC in chick embryos. We demonstrate that although early myogenesis is CNC-independent, the migration, patterning and differentiation of muscle precursors are regulated by CNC. In the absence of CNC cells, accumulated myoblasts are kept in a proliferative state, presumably because of an increase of Fgf8 in adjacent tissues, which leads to abnormalities in both differentiation and subsequent myofiber organization in the head. These results have uncovered a surprising degree of complexity and multiple distinct roles for CNC in the patterning and differentiation of muscles during craniofacial development. We suggest that CNC cells control craniofacial development by regulating positional interactions with mesoderm-derived muscle progenitors that together shape the cranial musculoskeletal architecture in vertebrate embryos.
