Dmef2, D-mef2, Myocyte enhancing factor 2, Mef-2, Dmef
Stop-codon suppression (UAG) postulated; FBrf0216885.
Gene model reviewed during 5.44
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.49
Gene model reviewed during 6.31
None of the polypeptides share 100% sequence identity.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Mef2 using the Feature Mapper tool.
Mef2 are detected throughout embryogenesis on northern blots with the highest levels in 4-8 and 8-12 hr embryos. Transcripts are first detected by in situ hybridization in the mesoderm primordium in stage 5 embryos. The expression is not uniform but occurs in a pair rule-like pattern of seven stripes. In stages 7 and 8, Mef2 expression occurs throughout the mesoderm. By stages 8 and 9, the pattern becomes very dynamic. Expression is higher in the dorsal region of the mesoderm than ventrally. By stage 9, patches of expression are seen in the dorsal region of the mesoderm with stripes that extend back toward the midline. In stages 10 and 11, expression is also observed in isolated groups of cells that may be heart precursors in one case, and somatic muscle founder cells in another. By stage 11, prominent expression is seen in progenitors of the visceral musculature and in cells that may contribute to the fat body. Later, Mef2 expression is observed in all muscle types. It is expressed in the three major groups of somatic muscles, the dorsal, lateral and ventral. It is expressed in the pharyngeal muscles of the head and in the visceral muscles of the esophagus, foregut, midgut and hindgut. It is also expressed in the heart in the cardioblasts but not in the pericardial cells. The expression pattern of Mef2 was compared to that of twi.
Mef2 transcripts are first detected in the ventral furrow during gastrulation. During germ band extension, Mef2 transcripts are limited to the mesodermal layer. In early stage 10 embryos, transcripts are in a single layer of mesoderm in cells that will give rise to pharyngeal muscle. Later in stage 10, the mesoderm separates into two cell layers. Mef2 transcripts are expressed in both the inner layer that gives rise to visceral muscle and heart precursor cells and the outer layer which gives rise to the somatic musculature. Expression is also high in pharyngeal muscle precursors. During germ band retraction, transcripts remain at high levels in the somatic musculature but decline in the visceral muscle and heart precursor cells. In late embryos, transcripts are observed in the somatic musculature and in the dorsal vessel but not in other mesoderm derivatives. Little or no Mef2 expression is observed in stage 11-12 sna or twi mutant embryos.
Mef2 transcripts are first detected in 0-4hr embryos, remain at significant levels throughout embryogenesis, decrease during larval stages, and increase during pupal stages. Transcripts are first detected at late cellular blastoderm stage and are expressed in all mesodermal cells after invagination. After dorsal migration of the mesodermal layer, expression is restricted to visceral muscle and heart primordia. Later expression is observed in heart precursors and then becomes prominant sequentially in visceral and somatic muscles. Mef2 expression is absent in twi mutant embryos and is only observed at low levels in germ band extended sna mutant embryos.
Comment: label visible in a superficial focal plane
Comment: contractile cells of dorsal vessel
Significantly higher levels of Mef2 expression are detected in s-LNv neurons towards the end of the night (ZT21) than the end of day (ZT9), but levels remain the same if the animals are kept in dark-dark conditions.
Mef2 protein is expressed in all contractile cells of the embryonic dorsal vessel
All myoblasts in the embryonic dorsal vessel express Mef2 protein.
Mef2 protein is localized to the nuclei of all embryonic somatic and visceral muscle cells and muscle cell precursors.
Mef2 is present in the nuclei of all muscular dorsal vessel cells of the embryo. A repeating pattern of six pairs of Mef2-positive cardial cells per segment was seen in the larval heart and each ostium is flanked closely by two of these cells.
Mef2 protein expression is detected throughout the mesoderm during germ band extension. After subdivision of the mesoderm, expression is observed in the cephalic mesoderm and in the primordia for the somatic and visceral musculature. Throughout germ band retraction and in older embryos, Mef2 protein expression persists in the visceral and pharyngeal musculature, as well as in the cardial cells and is detected in segmentally repeating groups of forming somatic muscles.
Mef2 expression is first detected in mesodermal cells in the ventral furrow during cellular blastoderm. During germband extension, it is expressed throughout the mesoderm. From stage 11, it is expressed in all of the muscle precursor cells as well as in the cardioblast cells. Expression becomes restricted to muscle cells and marks all of the muscle cells and their descendents in the embryo.
GBrowse - Visual display of RNA-Seq signalsView Dmel\Mef2 in GBrowse 2
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Mef2 is required for myoblast fusion and for the initiation of muscle structural gene expression during adult myogenesis.
Lateral transverse muscles of the thorax contain more Mef2 positive nuclei than those of the abdomen.
Mef2 transcription is controlled by a complex enhancer 5.8kb upstream of the gene, containing 2 tin binding sites. tin has an essential role in activation of Mef2 transcription in multiple myogenic lineages.
There is a Mef2 activity range compatible with proper muscle differentiation in the embryo. Distinct Mef2 protein thresholds are required for different properties within a muscle cell and also for different cells within a muscle type and for different muscle types.
Mef2 is required for the normal patterning and differentiation of the centripetally migrating follicle cells that are crucial for the development of the anterior chorionic structures.
Mef2 function is required for splitting of the larval oblique muscles that form the templates of the adult dorsal longitudinal indirect flight muscles.
twi protein directly regulates Mef2 expression in adult somatic muscle precursor cells via a 175bp enhancer located 2245bp upstream of the Mef2 transcriptional start site. Activation of Mef2 transcription via this enhancer by twi protein is essential for normal adult muscle development.
Tm2 is a target gene for Mef2 regulation, proximal and distal muscle enhancers within the first intron of Tm2 contain a Mef2 binding site. Mef2 is a positive regulator of Tm2 gene transcription that is necessary but not sufficient for high level expression in somatic muscle of the embryo, larva and adult.
Connections between motoneurons and muscles are formed in the absence of Mef2 function, but further differentiation of these contacts into mature neuromuscular junctions (NMJ) fails. The development of normal synaptic contacts with localised active zones appears to depend on properties of differentiating muscles that are absent in Mef2 mutant embryos.
The role of Mef2 is characterised using genetic mutations that result in loss of Mef2 function. In Mef2- embryos somatic mesoderm is formed normally and somatic muscle precursor cells initiate development, but continuing differentiation of the precursors into multinucleate muscle fibres requires Mef2 function. This can be rescued by providing exogenous Mef2 activity in the somatic mesoderm indicating that Mef2 function is essential for myogenesis. Midgut morphogenesis and late heart differentiation are also affected in Mef2 mutants.
Mef2 is required for differentiation of somatic, cardiac and visceral muscle cells, though not for the specification and positioning of myoblasts.
In the somatic muscle lineage Mef2 is required for both the formation and patterning of body wall muscle. Mef2 is also involved in the regulation of muscle specific gene expression in the dorsal vessel and midgut.
In the absence of Mef2 activity the midgut exhibits an abnormal bloated morphology. The midgut defect correlates with the absence of αPS2 integrin gene expression and suggests a regulatory relationship between Mef2 and the if locus which encodes this integrin subunit.
Mef2 is required for both the formation and patterning of the body wall muscle. Mutants show extensive apoptosis among the myoblast cell population. Morphogenesis of the dorsal vessel proceeds normally, but the myosin genes are not expressed. Mutants also exhibit an abnormal midgut morphology, which correlates with absence of if gene expression. Rare transheterozygous mutant survivors cannot fly.
Mef2 is the only known gene expressed in both the segregating primordia and the differentiated cells of the somatic, visceral and heart musculature.
Identification: Isolated from a 4 to 8 hour Drosophila embryo cDNA library, using a fragment encoding the DNA-binding and dimerisation domain of Xenopus SL-1, under low stringency conditions.
Temporal and spatial expression pattern of Mef2 suggests the gene product may play an important role in commitment of mesoderm to myogenic lineages.
Mef2 may have a function in early mesoderm differentiation and may be required for subsequent cell fate specifications within the somatic and visceral/heart mesodermal layers.