E2F function in muscle growth is necessary and sufficient for viability in Drosophila

• Published in: Nature communications Vol. 7; no. 1; p. 10509
• Main Authors: Zappia, Maria Paula, Frolov, Maxim V.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.01.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 14/1; 14/19; 38/77; 38/89; 631/136/2060/2068; 631/80/86; 64/24; 692/4023/1671/1668/1973; Adults; Animals; Cell cycle; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; E2F1 Transcription Factor - genetics; E2F1 Transcription Factor - metabolism; E2F2 Transcription Factor - genetics; E2F2 Transcription Factor - metabolism; Female; Gene Expression Regulation, Developmental - physiology; Gene Knockdown Techniques; Genes; Humanities and Social Sciences; Insects; Larva; Male; multidisciplinary; Muscle Development - genetics; Muscles - embryology; Musculoskeletal system; Pupa; Science; Science (multidisciplinary); Trans-Activators - genetics; Trans-Activators - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10509

The E2F transcription factor is a key cell cycle regulator. However, the inactivation of the entire E2F family in Drosophila is permissive throughout most of animal development until pupation when lethality occurs. Here we show that E2F function in the adult skeletal muscle is essential for animal viability since providing E2F function in muscles rescues the lethality of the whole-body E2F-deficient animals. Muscle-specific loss of E2F results in a significant reduction in muscle mass and thinner myofibrils. We demonstrate that E2F is dispensable for proliferation of muscle progenitor cells, but is required during late myogenesis to directly control the expression of a set of muscle-specific genes. Interestingly, E2f1 provides a major contribution to the regulation of myogenic function, while E2f2 appears to be less important. These findings identify a key function of E2F in skeletal muscle required for animal viability, and illustrate how the cell cycle regulator is repurposed in post-mitotic cells. 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 Drosophila skeletal muscle, with the contribution of E2f1 being most important in post-fusion muscle.