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The Drosophila FUS ortholog cabeza promotes adult founder myoblast selection by Xrp1-dependent regulation of FGF signaling


Autoři: Marica Catinozzi aff001;  Moushami Mallik aff001;  Marie Frickenhaus aff002;  Marije Been aff001;  Céline Sijlmans aff001;  Divita Kulshrestha aff001;  Ioannis Alexopoulos aff004;  Manuela Weitkunat aff005;  Frank Schnorrer aff005;  Erik Storkebaum aff001
Působiště autorů: Department of Molecular Neurobiology, Donders Institute for Brain, Cognition and Behaviour and Faculty of Science, Radboud University, Nijmegen, Netherlands aff001;  Molecular Neurogenetics Laboratory, Max Planck Institute for Molecular Biomedicine, Muenster, Germany aff002;  Faculty of Medicine, University of Muenster, Muenster, Germany aff003;  General Instruments Department, Faculty of Science, Radboud University, Nijmegen, Netherlands aff004;  Muscle Dynamics Group, Max Planck Institute of Biochemistry, Martinsried, Germany aff005;  Aix Marseille University, CNRS, IBDM, Marseille, France aff006
Vyšlo v časopise: The Drosophila FUS ortholog cabeza promotes adult founder myoblast selection by Xrp1-dependent regulation of FGF signaling. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008731
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008731

Souhrn

The number of adult myofibers in Drosophila is determined by the number of founder myoblasts selected from a myoblast pool, a process governed by fibroblast growth factor (FGF) signaling. Here, we show that loss of cabeza (caz) function results in a reduced number of adult founder myoblasts, leading to a reduced number and misorientation of adult dorsal abdominal muscles. Genetic experiments revealed that loss of caz function in both adult myoblasts and neurons contributes to caz mutant muscle phenotypes. Selective overexpression of the FGF receptor Htl or the FGF receptor-specific signaling molecule Stumps in adult myoblasts partially rescued caz mutant muscle phenotypes, and Stumps levels were reduced in caz mutant founder myoblasts, indicating FGF pathway deregulation. In both adult myoblasts and neurons, caz mutant muscle phenotypes were mediated by increased expression levels of Xrp1, a DNA-binding protein involved in gene expression regulation. Xrp1-induced phenotypes were dependent on the DNA-binding capacity of its AT-hook motif, and increased Xrp1 levels in founder myoblasts reduced Stumps expression. Thus, control of Xrp1 expression by Caz is required for regulation of Stumps expression in founder myoblasts, resulting in correct founder myoblast selection.

Klíčová slova:

Abdominal muscles – Immunostaining – Motor neurons – Muscle functions – Myoblasts – Neurons – Phenotypes – Pupae


Zdroje

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