Drosophila MEF2, a transcription factor that is essential for myogenesis.

Abstract

mef2 encodes the only apparent Drosophila homolog of the vertebrate myocyte-specific enhancer factor 2 (MEF2). We show herein that the Drosophila MEF2 protein is expressed throughout the mesoderm following gastrulation. Later in embryogenesis, its expression is maintained in precursors and differentiated cells of the somatic and visceral musculature, as well as the heart. We have characterized genetic deficiencies and EMS-induced point mutations that result in complete loss of MEF2 protein in homozygous mutant embryos. These embryos exhibit a dramatic absence of myosin heavy chain (MHCJ-expressing myoblasts and lack differentiated muscle fibers. Examination of earlier events of muscle development indicates that the specification and early differentiation of somatic muscle precursors are not affected because even-skipped-, nautilus., and/33-tubu/in-expressing myoblasts are present. However, these partially differentiated cells are unable to undergo further differentiation to form muscle fibers in the absence of me[2. The later aspects of differentiation of the visceral mesoderm and the heart are also disrupted in me[2 mutant embryos, although the specification and early development of these tissues appear unaffected. Midgut morphogenesis is disrupted in the mutant embryos, presumably as a consequence of abnormal development of the visceral mesoderm. In the heart, the cardial cells do not express MHC. These results indicate that MEF2 is required for later aspects of differentiation of the three major types of musculature, which include body wall muscles, gut musculature, and the heart, in the Drosophila embryo.

Conditional mutations in SERCA, the Sarco-endoplasmic reticulum Ca2+-ATPase, alter heart rate and rhythmicity in Drosophila

“…For experiments that involved detergent extraction of membrane prior to fixation, animals were dissected in normal saline and then incubated for 5 minutes in CSK buffer (10 mmolar PIPES, 100 mmolar KCl, 300 mmolar Sucrose, 2.5 mmolar MgCl [2], 1 mmolar PMSF, 1% aprotinin, and 1% Triton X-100). This was followed by normal fixation and staining procedures as outlined above.…”

Transcription ofDrosophilaTroponin I Gene Is Regulated by Two Conserved, Functionally Identical, Synergistic Elements

“…Bourbon (Bourbon et al, 2002). Transcription factors null alleles mef2 , tin 346 , bin 22 , and minc A388 have been described previously (Azpiazu and Frasch 1993;Bour et al, 1995;Zaffran et al, 2001;Ruiz-Gomez et al, 2002). In(1)z ae (bx) , z 58g , and P{wϩLacZ}Trl s2325 fly stocks were obtained from the Drosophila stock center (University of Indiana, Bloomington, IN).…”

“…In vertebrates, three different genes (fast, slow, and cardiac), encode specialized forms of TnI, whereas in Drosophila, the single gene wings-up A encodes 10 TnI protein isoforms (Barbas et al, 1991). The gene is expressed shortly after the monolayer of mesodermal cells is determined by the sequential expression of twist, Dmef2, tinman, and other transcription factor-encoding genes (stages 6 -7 or 3-4 h of development) (Thisse et al, 1987;Azpiazu and Frasch, 1993;Bour et al, 1995;Lilly et al, 1995;Taylor, 2000). Muscle progenitor cells are determined immediately afterwards, and their descendants, the muscle founder cells, become recognizable by the end of stage 11 (7-8 h) (Carmena et al, 1995;.…”

Transcriptional regulation of the Drosophila melanogaster muscle myosin heavy-chain gene

“…The latter includes E-boxes that bind helix-loop-helix transcription factors and MEF2 sites that bind MEF2 protein (Bour et al, 1995;Lilly et al, 1995). E-boxes, MEF2 sites and their binding factors positively regulate vertebrate muscle gene expression as well (see Molkentin and Olson, 1996 for review).…”