InteractiveFly: GeneBrief

myoglianin: Biological Overview | References

Gene name - myoglianin

Synonyms -

Cytological map position - 102D4-102D4

Function - ligand

Keywords - glia, mesoderm, larval brain, neuronal remodeling, regulation of Ecdysone receptor

Symbol - myo

FlyBase ID: FBgn0026199

Genetic map position - chr4:711,890-716,675

Classification - Transforming growth factor-beta family

Cellular location - secreted

NCBI links: Precomputed BLAST | EntrezGene

Recent literature
Ishimaru, Y., Tomonari, S., Matsuoka, Y., Watanabe, T., Miyawaki, K., Bando, T., Tomioka, K., Ohuchi, H., Noji, S. and Mito, T. (2016). TGF-beta signaling in insects regulates metamorphosis via juvenile hormone biosynthesis. Proc Natl Acad Sci U S A [Epub ahead of print]. PubMed ID: 27140602
Although butterflies undergo a dramatic morphological transformation from larva to adult via a pupal stage (holometamorphosis), crickets undergo a metamorphosis from nymph to adult without formation of a pupa (hemimetamorphosis). Despite these differences, both processes are regulated by common mechanisms that involve 20-hydroxyecdysone (20E) and juvenile hormone (JH). JH regulates many aspects of insect physiology, such as development, reproduction, diapause, and metamorphosis. Consequently, strict regulation of JH levels is crucial throughout an insect's life cycle. However, it remains unclear how JH synthesis is regulated. This study reports that in the corpora allata of the cricket, Gryllus bimaculatus, Myoglianin (Gb'Myo), a homolog of Drosophila Myoglianin/vertebrate GDF8/11, is involved in the down-regulation of JH production by suppressing the expression of a gene encoding JH acid O-methyltransferase, Gb'jhamt. In contrast, JH production is up-regulated by Decapentaplegic (Gb'Dpp) and Glass-bottom boat/60A (Gb'Gbb) signaling that occurs as part of the transcriptional activation of Gb'jhamt. Gb'Myo defines the nature of each developmental transition by regulating JH titer and the interactions between JH and 20E. When Gb'myo expression is suppressed, the activation of Gb'jhamt expression and secretion of 20E induce molting, thereby leading to the next instar before the last nymphal instar. Conversely, high Gb'myo expression induces metamorphosis during the last nymphal instar through the cessation of JH synthesis. Gb'myo also regulates final insect size. Because Myo/GDF8/11 and Dpp/bone morphogenetic protein (BMP)2/4-Gbb/BMP5–8 are conserved in both invertebrates and vertebrates, the present findings provide common regulatory mechanisms for endocrine control of animal development.


Glia secrete myoglianin, a TGF-β ligand, to instruct developmental neural remodeling in Drosophila. Glial myoglianin upregulates neuronal expression of an ecdysone nuclear receptor that triggers neurite remodeling following the late-larval ecdysone peak. Thus glia orchestrate developmental neural remodeling not only by engulfment of unwanted neurites but also by enabling neuron remodeling (Awasaki, 2011).

To establish and refine functional neural circuits, neurons alter connections as the organism matures. In Drosophila, larval brain neural circuits are remodeled into adult ones during metamorphosis. Neurons forming functional larval neural circuits prune their neural projections by local degeneration in early metamorphosis and re-extend their neurites to form the adult-specific neural circuits. This phenomenon requires activation of TGF-β signaling in the remodeling neurons. TGF-β signaling upregulates expression of the B1 isoform of the ecdysone receptor (EcR-B1) at the late larval stage. The pruning of larval projections is then triggered by the steroid molting hormone ecdysone (Awasaki, 2011).

The activin-β gene (Actβ), which encodes a Drosophila activin/TGF-β family molecule, is expressed in the developing larval brain. Temporal inhibition of Actβ with its dominant-negative form or double-stranded RNA (dsRNA) partially suppresses the expression of EcR-B1 in the wandering larvae. In a previous study, it was proposed that Actβ is a candidate ligand for TGF-β signaling in neuronal remodeling (Zheng, 2003). However, the recently isolated Actβ null mutant, Actβed80 (Zhu, 2008), had no developmental defects in the remodeling of the mushroom body γ neurons. This observation excludes Actβ as a principal ligand for TGF-β–dependent remodeling of mushroom body neurons. In addition, the Actβ null mutant grows normally until the pharate adult stage (Zhu, 2008)., contrasting the embryonic lethality that results from the ubiquitous induction of the dominant-negative form or dsRNA of Actβ. These contradictory phenomena suggest that off-target effects occur when Actβ is suppressed with dominant-negative proteins or RNA interference (Awasaki, 2011).

Notably, myoglianin (myo), which encodes another Drosophila TGF-β ligand (Lo, 1999), is temporally expressed in the brain of third instar larvae. Although no myo transcripts could be detected in the brain of early larvae, intense signals for myo transcripts were seen in subsets of glial cells in the cortex and inner regions of the central brain after the mid third instar larval stage. myo is selectively expressed in two subtypes of larval glial cells: the larval cortex and astrocyte-like glial cells. The cortex glia surround the cell body of each mature neuron and the astrocyte-like glia infiltrate into brain neuropile. The glial processes of both types are in the vicinity of, if not directly contacting, the larval mushroom body γ neurons (Awasaki, 2011).

To determine whether myo governs mushroom body remodeling, the glial expression of myo was silenced by targeted RNAi. dsRNA or microRNA (miRNA) against myo was selectively expressed in glia using the pan-glial GAL4 driver repo-GAL4. myo transcripts were no longer detectable after induction of myo dsRNA in pan-glial cells. The pruning and re-extension of mushroom body γ axons were examined by immunostaining with antibody to Fasciclin 2 (Fas2). In wild-type animals, the perpendicular γ axonal branches in the larval mushroom body lobes are completely pruned by 18 h after puparium formation (APF). γ neurons subsequently re-extended axons horizontally to form the midline-projecting γ lobe in adult brains. This remodeling was blocked by pan-glial induction of myo RNAi. The perpendicular axonal branches of γ neurons persisted through early metamorphosis, and the abnormally retained larval neurites coexisted with the α/β lobes in the adult mushroom bodies that failed to remodel. Direct visualization of mushroom body γ neurons validated the above observations with antibody to Fas2. The myo-silenced brains, including their glial network, were otherwise grossly normal. These observations indicate that a loss of myo expression in glia has no detectable effect on glial cells but adversely affects mushroom body remodeling (Awasaki, 2011).

myo was knocked down using glial subtype–specific drivers. Notably, only cortex glia–specific silencing could marginally block mushroom body remodeling and elicit mild mushroom body lobe defects in about 60% of adult mushroom bodies. However, silencing myo in both larval cortex and astrocyte-like glia fully recapitulated the mushroom body remodeling defects caused by the pan-glial induction of myo RNAi. These findings indicate that myo from two glial sources acts redundantly to govern mushroom body remodeling (Awasaki, 2011).

Next, to determine whether glial-derived myo is required for upregulation of EcR-B1 in remodeling mushroom body γ neurons, EcR-B1 expression in late-larval mushroom bodies in wild-type larvae was compared with expression in myo RNAi larvae. Although the characteristic pattern of EcR-B1 enrichment was detected in wild-type larvae, no such enrichment was detected in myo RNAi-expressing larvae. For example, the strong nuclear signal of EcR-B1 in the mushroom body γ neurons was no longer discernible. When EcR-B1 expression was selectively restored in the mushroom body γ neurons of animals expressing myo RNAi in glia, no defect in mushroom body remodeling could be detected. These findings suggest that the neuronal phenotypes resulting from glial myo RNAi can be effectively rescued by neuronal induction of EcR-B1. These results indicate that the glia-derived Myo instructs mushroom body remodeling via upregulation of neuronal EcR-B1 (Awasaki, 2011).

Remodeling of larval olfactory projection neurons is under the control of the same TGF-β and ecdysone signaling as the mushroom body γ neurons (Marin, 2005). The loss of glial myo blocked EcR-B1 expression and neurite remodeling of projection neurons, and the remodeling defect was substantially rescued by projection neuron–specific induction of transgenic EcR-B1. These results suggest that glia-derived Myo acts broadly to pattern neuronal remodeling via upregulation of EcR-B1 (Awasaki, 2011).

Using an FRT-mediated inter-chromosomal recombination technique, a deletion mutant, myoΔ1 was generated. Organisms homozygous for myoΔ1 showed no developmental delay through the third instar larval stage. However, mutant larvae prepupate on the surface of or in the food and are developmentally arrested before head inversion. In the myo mutant pupae (0 h APF) or prepupae (2–6 h APF), no enhancement of EcR-B1 expression was detected in the clustered cell bodies of mushroom body γ neurons. When myo expression was restored using myo-GAL4 to drive UAS-myo, the myo mutants grew into pharate or eclosed adults. These animals showed enriched EcR-B1 in the larval brain and they underwent normal mushroom body remodeling. In contrast, when myo expression was restored with myo-GAL4, but excluded in glia by using repo-GAL80 to selectively block GAL4 function in all glial cells, no enrichment of EcR-B1 was detected in the late larval or prepupal brains, and no evidence was found of neuronal remodeling in the pharate adults. These results with myo null mutants substantiate the notion that myo expression in glia governs neuronal remodeling via upregulation of neuronal EcR-B1 expression (Awasaki, 2011).

Does Myo activate TGF-β signaling through the Baboon (Babo) receptor that, contrasting with Myo, acts cell-autonomously to enable neuronal remodeling? There are three Babo isoforms with different ligand-binding domains (Jensen, 2009). Babo-A has been implicated in governing neuron remodeling. To determine whether Myo activity requires Babo-A, their relationship was examined by epistasis. Ubiquitous expression of Myo induced larval lethality. If Myo signals through Babo-A, silencing babo-A should suppress the Myo-induced larval lethality. Attempts were made to deplete specific Babo isoforms by miRNAs to isoform-specific exons. Targeted induction of babo-A miRNA, but not babo-B or babo-C miRNA, effectively blocked mushroom body remodeling. When such isoform-specific miRNAs were co-induced with the myo transgene, only miRNA against babo-A potently suppressed the larval lethality that resulted from ectopic Myo expression. These epistasis results provide in vivo evidence that Myo and Babo-A act in a linear pathway to upregulate EcR-B1 and enable neuronal remodeling (Awasaki, 2011).

Remodeling of larval neurons occurs promptly as the larvae cease activity and become pupae. The tight temporal control of this developmental neuronal remodeling requires a timely induction of the EcR-B1 in these neurons. Three pathways, including TGF-β signaling, the cohesin protein complex and the FTZ-F1 nuclear receptor, are essential for the late-larval upregulation of EcR-B1. The nature and source of the TGF-β signaling become increasingly clear with the finding that Myo, in addition to Babo and dSmad2, is indispensable for the upregulation of EcR-B1. Myo can bind with the Babo/Wit receptor complex in culture (Lee-Hoeflich, 2005). Notably, Myo is produced by glia and is required in glia for neuronal expression of EcR-B1. Namely, glial cells directly instructed the neural remodeling through secretion of Myo. Glial cells further participate in the execution of neuronal remodeling through facilitation of neurite pruning by engulfment of the unwanted neuronal processes. Thus, glial cells orchestrate developmental neural remodeling and may have active roles in dynamically modulating mature neuronal connections (Awasaki, 2011).

Myostatin-like proteins regulate synaptic function and neuronal morphology

Growth factors of the TGF-beta superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of both Myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. This study shows that Myoglianin (MYO), the Drosophila homolog of Myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner. Both Myostatin and GDF11 affected synapse formation in isolated rat cortical neuron cultures, suggesting an effect on synaptogenesis beyond neuromuscular junctions. This study also shows that Myoglianin acts in vivo to inhibit synaptic transmission between neurons in the escape response neural circuit of adult flies. Thus, these anti-myogenic proteins act as important inhibitors of synapse function and neuronal growth (Augustin, 2017).

Growth factors regulate many aspects of tissue development, growth and metabolism. Myostatin and GDF11 are highly homologous members of the TGF-β superfamily of growth factors. While GDF11 plays a role in a variety of systems, the role of Myostatin appears to be confined to skeletal and cardiac muscles (Augustin, 2017).

Despite the previously described roles of MYO in neural remodelling and synapse refinement (Awasaki, 2011; Yu, 2013) very little is known about the impact of Myoglianin on synaptic physiology. This study first established muscle-derived MYO as a negative regulator of both spontaneous and evoked response at the NMJ, demonstrating its role as a broad regulator of synaptic transmission. The highly coordinated apposition of active zones and glutamate receptors underlies their ability to regulate synaptic strength and plasticity of the larval NMJ. This study has shown that muscle expression of myo inversely affects the NMJ quantity of Brp and GluRIIA, critical pre-and post-synaptic proteins, and determinants of evoked neurotransmitter release and quantal size (i.e., postsynaptic sensitivity to presynaptically released transmitter), respectively. While it is possible that MYO exerts its influence on synaptic strength through other mediators, GluRIIA and Brp are their likely downstream effectors. The electrophysiological results, obtained using the GAL4-UAS system for targeted manipulation of myo, differ from the ones obtained recently using a genetic null myo mutant showing slightly reduced miniature amplitudes (Kim, 2014). The likely explanation is that compensatory effects happen in other tissues in the tissue-specific knockdown animals that cannot occur in genetic nulls, especially for systemic type factors. The other possible explanation is differential cross regulation between different (MYO-like) ligands in genetic null vs tissue knockdown animals. These results thus indicate the relevance of tissue specificity of MYO action, and of myo expression levels, in regulating synaptic function, and emphasize the need for caution when interpreting results from different types of gene manipulations (Augustin, 2017).

myo expression was detected in the glial cells of the larval neuromuscular junction. While Drosophila NMJ contains at least 2 subtypes of glia, myo expression appears confined to the 'repo-positive' subtype both in the central (Awasaki, 2011) and peripheral nervous system. The dual muscle and glial presence makes MYO ideally positioned for regulating NMJ function. Due to the small size of the compartment, however, glia-derived MYO likely has a modulatory role at the neuromuscular junction (Augustin, 2017).

This study also found that muscle suppression of Myoglianin, a Drosophila homolog of Myostatin and GDF11, promotes increased larval weight and body-wall muscle size in developing larvae, resembling the effect of Myostatin knockdown in mammals. Interestingly, pan-glial expression of myo negatively affected larval wet weight, but not the size of somatic myofibers, suggesting previously unsuspected systemic roles for glial cells (Augustin, 2017).

Smad2 is a mediator of MYO action on both evoked response and postsynaptic sensitivity, with MAD having a minor effect on the latter. While MAD primarily functions as a cytoplasmic transducer of BMP signalling, it has been demonstrated that, under certain conditions, MAD can be phosphorylated in response to Activin pathway activation (Peterson, 2012; Augustin, 2017 and references therein).

This study detected elevated levels of phosphorylated Akt and GSK-3/Shaggy in larval somatic muscles of animals with reduced myo expression in this tissue. In flies and mammals, the Akt- mTOR axis promotes skeletal muscle growth, and phosphorylation-induced inhibition of GSK-3/Shaggy induces hypertrophy in skeletal myotube. The effects of attenuated myo expression on larval tissue size, however, do not appear to be mediated by Smad2 (or MAD) activation as their overexpression does not reverse the weight phenotype in 'low myo' background. Indeed, 'non-Smad' signalling pathways have been demonstrated for various TGF-β ligands in vertebrates and Drosophila. In addition to its role as an inhibitor of the NMJ growth and active zone formation in developing Drosophila larvae, GSK-3β is also a critical promoter of synaptic plasticity, possibly through regulation of glutamate receptor function or trafficking. This work has revealed Shaggy as a mediator of reduced MYO action, and as a negative regulator of synaptic strength at the larval NMJ. While MYO likely affects both sides of the synapse directly, an unlikely but possible scenario is that presynaptic motoneuron responds to a retrograde signal released from muscle/glial cells at the NMJ in response to an induction by MYO. An attractive hypothesis is that MYO negatively regulates presynaptic release directly, in conjunction with muscle-secreted Gbb, a positive regulator of neuromuscular synapse development and growth. The effects of MYO could also be mediated through the transmembrane protein Plum, previously proposed to regulate connectivity at the larval NMJ by sequestrating Myoglianin (Yu, 2013; Augustin, 2017 and references therein).

Myostatin negatively regulates synaptic function and neuronal morphology This study found that injections of Myostatin into rapidly growing larvae abolish the positive effect of myo down-regulation on NMJ strength and composition, and reverse the elevated muscle p-Akt levels. Furthermore, both Myostatin and GDF11 surpressed the growth of neuronal processes and perturbed the formation of synapses in cultured brain neurons, suggesting a direct action on neurons and regulation of synaptogenesis beyond neuromuscular junctions. Recently, Myostatin transcript and protein were detected in the mouse hippocampus and olfactory system neurons, respectively, and Myostatin type I (Alk4/5) and type II (ActIIB) receptors were found to be expressed in the mammalian nervous system. The current results therefore expand on these findings, suggesting functional relevance for Myostatin in both peripheral and central nervous system, and beyond its action as a canonical regulator of skeletal muscle growth. These novel roles remain to be further explored (Augustin, 2017).

This study expanded analysis of the functional relevance of MYO in the nervous system by demonstrating its importance in a non-NMJ synapse. Specifically, Myoglianin plays a role in the development of a mixed electro-chemical synapse in the Drosophila escape response pathway, likely by regulating the density of shakB-encoded gap junctions at the GF-TTMn synapse (Blagburn, 1999). These findings implicate MYO as a broad negative regulator of neuronal function across the nervous system and developmental stages (Augustin, 2017).

This work thus reveals broad and novel roles for anti-myogenic TGF-β superfamily of proteins in the nervous system and suggests new targets for interventions into synaptic function across species (Augustin, 2017).

Intertissue control of the nucleolus via a myokine-dependent longevity pathway

Recent evidence indicates that skeletal muscle influences systemic aging, but little is known about the signaling pathways and muscle-released cytokines (myokines) responsible for this intertissue communication. This study shows that muscle-specific overexpression of the transcription factor Mnt decreases age-related climbing defects and extends lifespan in Drosophila. Mnt overexpression in muscle autonomously decreases the expression of nucleolar components and systemically decreases rRNA levels and the size of the nucleolus in adipocytes. This nonautonomous control of the nucleolus, a regulator of ribosome biogenesis and lifespan, relies on Myoglianin<, a myokine induced by Mnt and orthologous to human GDF11 and Myostatin. Myoglianin overexpression in muscle extends lifespan and decreases nucleolar size in adipocytes by activating p38 mitogen-activated protein kinase (MAPK), whereas Myoglianin RNAi in muscle has converse effects. Altogether, these findings highlight a key role for myokine signaling in the integration of signaling events in muscle and distant tissues during aging (Demontis, 2014. PubMed ID: 24882005).

Distinct signaling of Drosophila Activin/TGF-β family members

Growth factors of the TGF-beta family signal through type I/II receptor complexes that phosphorylate SMAD transcription factors. This study analyzed signaling of all seven TGF-beta members to identify those that mediate growth through the Drosophila type I receptor BABO. It was found that two potential ligands of BABO, Myoglianin (MYO) and Maverick (MAV), do not activate dSMAD2. Only Drosophila Activin (dACT) and the Activin-like ligand Dawdle (DAW) signal through BABO in combination with the type II receptor PUNT and activate dSMAD2. Surprisingly, it was found that activation of BABO can also lead to the phosphorylation of the 'BMP-specific' MAD. In wing discs, expression of an activated form of dSMAD2 promotes growth similar to dACT and activated BABO. By itself, activated dSMAD2 does not affect DPP/GBB target genes. However, coexpression of activated forms of dSMAD2 and MAD additively induces the expression of spalt. In contrast to dACT, it was found that DAW does not promote growth when expressed in wings. In fact, coexpression of DAW with MAD or dSMAD2 decreases growth. daw mutants die primarily during larval stages and exhibit anal pad phenotypes reminiscent of babo mutants. The rescue of daw mutants by restricted expression in neuroendocrine cells indicates that Activin-type ligands are likely distributed through the endocrine system. The distinct signaling of dACT, DAW and MYO through BABO suggests the existence of co-receptors that modulate the canonical SMAD pathway (Gesualdi, 2007; full text of article).

The Drosophila type II receptor, Wishful thinking, binds BMP and myoglianin to activate multiple TGFβfamily signaling pathways

Wishful thinking (Wit) is a Drosophila transforming growth factor-β (TGFβ) superfamily type II receptor most related to the mammalian bone morphogenetic protein (BMP) type II receptor, BMPRII. To better understand its function, a biochemical approach was undertaken to establish the ligand binding repertoire and downstream signaling pathway. It was observed that BMP4 and BMP7, bound to receptor complexes comprised of Wit and the type I receptor Thickveins and Saxophone to activate a BMP-like signaling pathway. Further it was demonstrated that both Myoglianin and its most closely related mammalian ligand, Myostatin, interacted with a Wit and Baboon (Babo) type II-type I receptor complex to activate TGFβ/activin-like signaling pathways. These results thereby demonstrate that Wit binds multiple ligands to activate both BMP and TGFβ-like signaling pathways. Given that Myoglianin is expressed in muscle and glial-derived cells, these results also suggest that Wit may mediate Myoglianin-dependent signals in the nervous system (Lee-Hoeflich, 2005).

To provide insight into the molecular mechanisms of Wit that contribute to the biological functions of Wit, this study has characterized the Wit interacting ligands, their compatible type I receptor partners, and their downstream signaling pathways. The binding of BMP7, the mammalian ligand most related to Gbb, to Wit is in agreement with and gives biochemical evidence for results obtained from genetic analysis indicating that Wit mediates Gbb-activated BMP signaling in collaboration with the type I receptors, Tkv and Sax. The demonstration of the binding of BMP4, a functional ortholog of Dpp, to the receptor complex also suggests the possibility of Wit mediating Dpp signals. Dpp is not expressed in muscle or motoneurons but Wit is widely expressed in the central nervous system from embryonic stages suggesting that this putative Dpp signaling might regulate early developmental processes other than NMJ formation. The data showing that a receptor complex comprised of Wit and Tkv can activate MAD phosphorylation is also in agreement with the observation of impaired phosphorylation of MAD in Wit deficient flies and provides further support for a role of Wit in mediating BMP signaling (Lee-Hoeflich, 2005).

While the expression of dActivin in the developing nervous system and its proposed function in neuronal remodeling downstream of Wit or Punt have led to a suggestion that dActivin might induce Wit-mediated activin signaling, this study observed that mammalian activin, which is most closely related to dActivin, does not bind to Wit. One possible explanation for this discrepancy is that Wit might bind ligands other than dActivin and that this indirectly compensates for the lack of Punt-dActivin interaction. An attempt to produce dActivin in mammalian cells using a heterologous system was unsuccessful, thus the possibility cannot be eliminated that mammalian and Drosophila activins have different binding specificities. Generation of dActivin null flies or cell clones and testing for functional equivalence in rescue experiments should help resolve this issue (Lee-Hoeflich, 2005).

Alternatively, it is speculated that Wit might mediate activin signaling via Myoglianin since myostatin, the mammalian ligand most closely related to Myoglianin, activates a TGFβ/activin-like pathway. Accordingly, it was found that both myoglianin and myostatin bind to the Wit and Babo receptor complex. Furthermore, it was observed that coexpression of Wit and Babo induces dSmad2 phosphorylation and mediates myostatin-induced transcriptional activation of a TGFβ/activin-responsive reporter. In agreement to these observations, ectopic expression of Wit induces dSmad2 phosphorylation in insect S2 cells. Retrograde signaling between target-derived factors and the presynaptic terminal is crucial for NMJ development. Since Drosophila Myoglianin is abundantly expressed in muscle at late developmental stages and since Wit-mediated retrograde signaling had been identified previously, it is postulated that Myoglianin might activate a novel retrograde Wit signaling pathway. Interestingly, myostatin inhibits the BMP7 signaling response by competitive binding to type II receptor, ActRIIB, thus the binding of Myoglianin to Wit might also affect Gbb-mediated signaling and thus contribute to NMJ formation. Generation of flies harboring myoglianin loss-of-function mutations will shed light on these issues. These observations underscore the diverse mechanisms controlling Wit signaling and add impetus to further experiments in the context of the Wit receptor (Lee-Hoeflich, 2005).

Sequence and expression of myoglianin, a novel Drosophila gene of the TGF-beta superfamily

Various members of the TGF-beta superfamily of signaling molecules are known to have important roles in mesoderm patterning and differentiation during vertebrate and invertebrate embryogenesis. This study has characterize a new TGF-beta member from Drosophila, Myoglianin, that is most closely related to the vertebrate muscle differentiation factor Myostatin and to vertebrate BMP-11. Northern analysis shows that myoglianin is expressed throughout the Drosophila life cycle. In situ hybridization detects maternally-derived transcripts that are enriched in the pole plasm and later become enclosed in the pole cells. Between stages 11 and 14, myoglianin mRNA is exclusively detected in glial cells and their precursors. Following stage 14, high levels of myoglianin expression are observed in the developing somatic muscles as well as in visceral muscles and cardioblasts. It was also shown that the zygotic expression of the recently described Drosophila activinβ, which maps to the same interval on chromosome 4 as myoglianin, is restricted to the developing central and peripheral nervous system (Lo, 1999).

Using in situ hybridization, the pattern of myoglianin expression was examined during Drosophila development. In preblastoderm embryos, a high level of maternally-deposited myoglianin transcripts is uniformly distributed throughout the embryo, with an even higher localization at the very posterior end. This posterior concentration of message appears to be in the pole plasm since embryos laid by females homozygous for the oskar6 mutation lack pole plasm and do not show localization of myoglianin transcripts at the posterior. In stage 6 gastrulation embryos, the localized pole plasm message appears to be incorporated into pole cells, while the overall level of maternal transcript in the rest of the embryo has decreased. Zygotic expression of myoglianin is first observed in stage 11 embryos in what appear to be glial precursor cells. By stage 14, strong expression is evident in glial cells (CNS and exit/peripheral glia). This glial expression of myoglianin is completely lost in stage 15 embryos and expression is now detected in the somatic, visceral, and heart musculature, which then persists through late embryogenesis. In third instar larvae, the only specific pattern of expression observed is in the brain and ventral nerve cord, where a particular subset of cells, presumably glial cells, express myoglianin (Lo, 1999).

Functions of Myoglianin orthologs in other species

Sexually dimorphic control of gene expression in sensory neurons regulates decision-making behavior in C. elegans

Animal behavior is directed by the integration of sensory information from internal states and the environment. Neuroendocrine regulation of diverse behaviors of Caenorhabditis elegans is under the control of the DAF-7/TGF-β (see Drosophila myo) ligand that is secreted from sensory neurons. This study shows that C. elegans males exhibit an altered, male-specific expression pattern (see Drosophila sex determination) of daf-7 in the ASJ sensory neuron pair with the onset of reproductive maturity, which functions to promote male-specific mate-searching behavior. Molecular genetic analysis of the switch-like regulation of daf-7 expression in the ASJ neuron pair reveals a hierarchy of regulation among multiple inputs-sex, age, nutritional status, and microbial environment-which function in the modulation of behavior. These results suggest that regulation of gene expression in sensory neurons can function in the integration of a wide array of sensory information and facilitate decision-making behaviors in C. elegans (Hilbert, 2017).


Search PubMed for articles about Drosophila Myoglianin

Augustin, H., McGourty, K., Steinert, J. R., Cocheme, H. M., Adcott, J., Cabecinha, M., Vincent, A., Halff, E. F., Kittler, J. T., Boucrot, E. and Partridge, L. (2017). Myostatin-like proteins regulate synaptic function and neuronal morphology. Development 144(13):2445-2455. PubMed ID: 28533206

Awasaki, T., Huang, Y., O'Connor, M. B. and Lee, T. (2011). Glia instruct developmental neuronal remodeling through TGF-β signaling. Nat. Neurosci. 14(7):821-3. PubMed ID: 21685919

Blagburn, J. M., Alexopoulos, H., Davies, J. A. and Bacon, J. P. (1999). Null mutation in shaking-B eliminates electrical, but not chemical, synapses in the Drosophila giant fiber system: a structural study. J Comp Neurol 404(4): 449-458. PubMed ID: 9987990

Demontis, F., Patel, V. K., Swindell, W. R. and Perrimon, N. (2014). Intertissue control of the nucleolus via a myokine-dependent longevity pathway. Cell Rep 7(5):1481-94. PubMed ID: 24882005

Gesualdi, S. C. and Haerry, T. E. (2007). Distinct signaling of Drosophila Activin/TGF-beta family members. Fly (Austin). 1(4): 212-21. PubMed ID: 18820452

Hilbert, Z.A. and Kim, D.H. (2017). Sexually dimorphic control of gene expression in sensory neurons regulates decision-making behavior in C. elegans. Elife 6. PubMed ID: 28117661

Jensen, P. A., Zheng, X., Lee, T. and O'Connor, M. B. (2009). The Drosophila Activin-like ligand Dawdle signals preferentially through one isoform of the Type-I receptor Baboon. Mech. Dev. 126: 950-957. PubMed ID: 19766717

Kim, M. J. and O'Connor, M. B. (2014). Anterograde Activin signaling regulates postsynaptic membrane potential and GluRIIA/B abundance at the Drosophila neuromuscular junction. PLoS One 9(9): e107443. PubMed ID: 25255438

Lee-Hoeflich, S. T., Zhao, X., Mehra, A., Attisano, L.T. (2005). The Drosophila type II receptor, Wishful thinking, binds BMP and myoglianin to activate multiple TGFbeta family signaling pathways FEBS Lett. 579: 4615-21. PubMed ID: 16098524

Lo, P. C. and Frasch, M. (1999). Sequence and expression of myoglianin, a novel Drosophila gene of the TGF-beta superfamily. Mech. Dev. 86(1-2): 171-5. PubMed ID: 10446278

Marin, E.C., Watts, R.J., Tanaka, N.K., Ito, K. and Luo, L. (2005). Developmentally programmed remodeling of the Drosophila olfactory circuit. Development 132: 725-737. PubMed ID: 15659487

Peterson, A. J., Jensen, P. A., Shimell, M., Stefancsik, R., Wijayatonge, R., Herder, R., Raftery, L. A. and O'Connor, M. B. (2012). R-Smad competition controls activin receptor output in Drosophila. PLoS One 7(5): e36548. PubMed ID: 22563507

Yu, X. M., Gutman, I., Mosca, T. J., Iram, T., Ozkan, E., Garcia, K. C., Luo, L. and Schuldiner, O. (2013). Plum, an immunoglobulin superfamily protein, regulates axon pruning by facilitating TGF-beta signaling. Neuron 78(3): 456-468. PubMed ID: 23664613

Zheng, X., et al. (2003). TGF-ß signaling activates steroid hormone receptor expression during neuronal remodeling in the Drosophila brain. Cell 112: 303-315. 12581521

Zhu, C. C., et al. (2008). Drosophila Activin-β and the Activin-like product Dawdle function redundantly to regulate proliferation in the larval brain. Development 135(3): 513-21. PubMed ID: 18171686

Biological Overview

date revised: 15 March 2017

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