Characterization ofDrosophila hibris, a gene related to human nephrin

Development ◽  
2001 ◽  
Vol 128 (21) ◽  
pp. 4265-4276 ◽  
Author(s):  
Heather A. Dworak ◽  
Michael A. Charles ◽  
Lidia B. Pellerano ◽  
Helen Sink
Keyword(s):  
Muscle Development ◽  
Attachment Site ◽  
Cell Aggregation ◽  
Myoblast Fusion ◽  
Immunoglobulin Superfamily ◽  
Somatic Muscle ◽  
Muscle Insertion ◽  
Fusion Competent Myoblasts ◽  
Cns Midline ◽  
Heterotypic Interaction

Hibris encodes a protein that is a newly identified member of the immunoglobulin superfamily and has homology to vertebrate Nephrins and Drosophila Sticks-and-Stones. The Hibris protein has eight Ig-like domains, a fibronectin domain and a 160 amino acid cytoplasmic tail. The hibris transcript is expressed in a broad range of tissues and across life stages. In the embryo, hibris transcript is present in the mesectoderm, then in a group of cells at the developing CNS midline and in a subset of glia. In the periphery, hibris is expressed by fusion competent myoblasts and the epidermal muscle attachment site cells. Deletion analyses show that loss of hibris does not visibly affect embryonic CNS or somatic muscle development. However overexpressing hibris in the somatic mesoderm disrupts myoblast fusion. Furthermore, when overexpressed in the epidermis, Hibris causes comprehensive derangement of muscle insertion locations. A similar myoblast fusion defect is observed when the Drosophila homologs of DM-GRASP/BEN/SC1 (irregular chiasm-roughest and dumbfounded) are deleted together. Our S2 cell aggregation assays have revealed a heterotypic interaction between Hibris and Dumbfounded, but not between Hibris and Irregular Chiasm-Roughest. We propose that Hibris is an extracellular partner for Dumbfounded and potentially mediates the response of myoblasts to this attractant.

who encodes a KH RNA binding protein that functions in muscle development

Development ◽  
1997 ◽  
Vol 124 (7) ◽  
pp. 1323-1332 ◽  
Author(s):  
E.H. Baehrecke
Keyword(s):  
Muscle Development ◽  
Rna Binding ◽  
Attachment Site ◽  
Dorsal Surface ◽  
Binding Motif ◽  
Muscle Attachment ◽  
Somatic Muscle ◽  
Steroid Signaling ◽  
And Behavior ◽  
Late Stages

The Drosophila who (wings held-out) gene functions during the late stages of somatic muscle development when myotubes migrate and attach to specific epidermal sites. Animals lacking who function are capable of forming multinucleate myotubes, but these cells are restricted in migration. who mutants die at the end of embryogenesis with the posterior end of their cuticles arrested over the dorsal surface. Animals that possess weak who mutations either die as pupae, or survive as adults with defects in wing position. These phenotypes indicate that who also functions during metamorphosis, when muscles are reorganized to support adult structures and behavior. These embryonic and metamorphosis defects are similar to the phenotypes produced by previously identified genes that function in either muscle development or steroid signaling pathways. who transcription occurs in muscle and muscle attachment site cells during both embryogenesis and metamorphosis, and is inducible by the steroid ecdysone at the onset of metamorphosis. who encodes a protein that contains a KH RNA binding domain. Animals that possess a mutation in a conserved loop that links predicted alpha and beta structures of this RNA binding motif lack who function. These results indicate that who plays an essential role in steroid regulation of muscle development.

scholarly journals Mechanisms of myoblast fusion during muscle development

2015 ◽  
Vol 32 ◽  
pp. 162-170 ◽  
Author(s):  
Ji Hoon Kim ◽  
Peng Jin ◽  
Rui Duan ◽  
Elizabeth H Chen
Keyword(s):  
Muscle Development ◽  
Myoblast Fusion

rolling pebbles(rols) is required inDrosophilamuscle precursors for recruitment of myoblasts for fusion

Development ◽  
2001 ◽  
Vol 128 (24) ◽  
pp. 5061-5073 ◽  
Author(s):  
Annette Rau ◽  
Detlev Buttgereit ◽  
Anne Holz ◽  
Richard Fetter ◽  
Stephen K. Doberstein ◽  
...  
Keyword(s):  
Amino Acids ◽  
Transcription Initiation ◽  
Muscle Development ◽  
Precursor Cells ◽  
Malpighian Tubules ◽  
Muscle Precursor ◽  
Terminal Amino ◽  
Founder Cells ◽  
Fusion Competent Myoblasts ◽  
Muscle Precursor Cells

Mutations in the rolling pebbles (rols) gene result in severe defects in myoblast fusion. Muscle precursor cells are correctly determined, but myogenesis does not progress significantly beyond this point because recognition and/or cell adhesion between muscle precursor cells and fusion-competent myoblasts is disturbed. Molecular analysis of the rols genomic region reveals two variant transcripts of rols due to different transcription initiation sites, rols6 and rols7. rols6 mRNA is detectable mainly in the endoderm during differentiation as well as in malpighian tubules and in the epidermis. By contrast, rols7 expression is restricted to the mesoderm and later to progenitor descendants during somatic and pharyngeal muscle development. Transcription starts at the extended germ band stage when progenitor/founder cells are determined and persists until stage 13. The proteins encoded by the rols gene are 1670 (Rols6) and 1900 (Rols7) amino acids in length. Both forms contain an N-terminal RING-finger motif, nine ankyrin repeats and a TPR repeat eventually overlaid by a coiled-coil domain. The longer protein, Rols7, is characterized by 309 unique N-terminal amino acids, while Rols6 is distinguishable by 79 N-terminal amino acids. Expression of rols7 in muscle founder cells indicates a function of Rols7 in these cells. Transplantation assays of rols mutant mesodermal cells into wild-type embryos show that Rols is required in muscle precursor cells and is essential to recruit fusion-competent myoblasts for myotube formation.

Autonomous and nonautonomous Notch functions for embryonic muscle and epidermis development in Drosophila

Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 617-626 ◽  
Author(s):  
R. Baker ◽  
G. Schubiger
Keyword(s):  
Muscle Development ◽  
N Gene ◽  
Somatic Muscle ◽  
Notch Protein ◽  
Proper Number ◽  
Cellular Domain ◽  
A Cell ◽  
Embryonic Muscle ◽  
Drosophila Embryos ◽  
Epidermal Development

The Notch (N) gene encodes a cell signaling protein that mediates neuronal and epidermal determination in Drosophila embryos. N also regulates several aspects of myogenic development; embryos lacking N function have too many muscle founder cells and fail to properly differentiate somatic muscle. To identify cell-autonomous requirements for Notch function during muscle development, we expressed a Notch minigene in the mesoderm, but not in the ectoderm, of amorphic N-embryos. In these embryos, muscle founder hypertrophy is rescued, indicating that Notch is autonomously required by mesoderm cells to regulate the proper number of muscle founders. However, somatic muscle differentiation is only partially normalized, suggesting that Notch is also required in the ectoderm for proper muscle development. Additionally, mesodermal expression of Notch partially rescues epidermal development in overlying neurogenic ectoderm. This is unexpected, since previous studies suggest that Notch is autonomously required by proneural ectoderm cells for epidermal development. Mesodermal expression of a truncated Notch protein lacking the extracellular domain does not rescue ventral epidermis, suggesting that the extra-cellular domain of Notch can non-autonomously rescue epidermal development across germ layers.

The role of the NK-homeobox gene slouch (S59) in somatic muscle patterning

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4525-4535 ◽  
Author(s):  
S. Knirr ◽  
N. Azpiazu ◽  
M. Frasch
Keyword(s):  
Muscle Development ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Drosophila Embryo ◽  
Loss Of Function ◽  
Cell Fates ◽  
Somatic Muscle ◽  
Gene Encoding ◽  
Body Wall Muscles ◽  
Founder Cells

In the Drosophila embryo, a distinct class of myoblasts, designated as muscle founders, prefigures the mature pattern of somatic body wall muscles. Each founder cell appears to be instrumental in generating a single larval muscle with a defined identity. The NK homeobox gene S59 was the first of a growing number of proposed ‘identity genes’ that have been found to be expressed in stereotyped patterns in specific subsets of muscle founders and their progenitor cells and are thought to control their developmental fates. In the present study, we describe the effects of gain- and loss-of-function experiments with S59. We find that a null mutation in the gene encoding S59, which we have named slouch (slou), disrupts the development of all muscles that are derived from S59-expressing founder cells. The observed phenotypes upon mutation and ectopic expression of slouch include transformations of founder cell fates, thus confirming that slouch (S59) functions as an identity gene in muscle development. These fate transformations occur between sibling founder cells as well as between neighboring founders that are not lineage-related. In the latter case, we show that slouch (S59) activity is required cell-autonomously to repress the expression of ladybird (lb) homeobox genes, thereby preventing specification along the lb pathway. Together, these findings provide new insights into the regulatory interactions that establish the somatic muscle pattern.

scholarly journals Indirect flight muscles in Drosophila melanogaster as a tractable model to study muscle development and disease

2020 ◽  
Vol 64 (1-2-3) ◽  
pp. 167-173
Author(s):  
Saroj Jawkar ◽  
Upendra Nongthomba
Keyword(s):  
Drosophila Melanogaster ◽  
Muscle Development ◽  
Myoblast Fusion ◽  
Successful Development ◽  
Adult Muscle ◽  
Attachment Sites ◽  
Flight Muscles ◽  
And Function

Myogenesis is a complex multifactorial process leading to the formation of the adult muscle. An amalgamation of autonomous processes including myoblast fusion and myofibrillogenesis, as well as non-autonomous processes, such as innervations from neurons and precise connections with attachment sites, are responsible for successful development and function of muscles. In this review, we describe the development of the indirect flight muscles (IFMs) in Drosophila melanogaster, and highlight the use of the IFMs as a model for studying muscle development and disease, based on recent studies on the development and function of IFMs.

scholarly journals Structure–function analysis of myomaker domains required for myoblast fusion

2016 ◽  
Vol 113 (8) ◽  
pp. 2116-2121 ◽  
Author(s):  
Douglas P. Millay ◽  
Dilani G. Gamage ◽  
Malgorzata E. Quinn ◽  
Yi-Li Min ◽  
Yasuyuki Mitani ◽  
...  
Keyword(s):  
Muscle Development ◽  
Function Analysis ◽  
Transmembrane Protein ◽  
Specific Protein ◽  
Biochemical Properties ◽  
Myoblast Fusion ◽  
Related Family ◽  
Membrane Spanning ◽  
Cellular Components ◽  
Heterologous Cell

During skeletal muscle development, myoblasts fuse to form multinucleated myofibers. Myomaker [Transmembrane protein 8c (TMEM8c)] is a muscle-specific protein that is essential for myoblast fusion and sufficient to promote fusion of fibroblasts with muscle cells; however, the structure and biochemical properties of this membrane protein have not been explored. Here, we used CRISPR/Cas9 mutagenesis to disrupt myomaker expression in the C2C12 muscle cell line, which resulted in complete blockade to fusion. To define the functional domains of myomaker required to direct fusion, we established a heterologous cell–cell fusion system, in which fibroblasts expressing mutant versions of myomaker were mixed with WT myoblasts. Our data indicate that the majority of myomaker is embedded in the plasma membrane with seven membrane-spanning regions and a required intracellular C-terminal tail. We show that myomaker function is conserved in other mammalian orthologs; however, related family members (TMEM8a and TMEM8b) do not exhibit fusogenic activity. These findings represent an important step toward deciphering the cellular components and mechanisms that control myoblast fusion and muscle formation.

scholarly journals Human Myoblast Fusion Requires Expression of Functional Inward Rectifier Kir2.1 Channels

2001 ◽  
Vol 153 (4) ◽  
pp. 677-686 ◽  
Author(s):  
Jacqueline Fischer-Lougheed ◽  
Jian-Hui Liu ◽  
Estelle Espinos ◽  
David Mordasini ◽  
Charles R. Bader ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Membrane Potential ◽  
Muscle Development ◽  
Myoblast Fusion ◽  
Inward Rectifier ◽  
Resting Membrane Potential ◽  
Skeletal Muscle Development ◽  
K Channels ◽  
Window Current ◽  
Human Myoblast

Myoblast fusion is essential to skeletal muscle development and repair. We have demonstrated previously that human myoblasts hyperpolarize, before fusion, through the sequential expression of two K+ channels: an ether-à-go-go and an inward rectifier. This hyperpolarization is a prerequisite for fusion, as it sets the resting membrane potential in a range at which Ca2+ can enter myoblasts and thereby trigger fusion via a window current through α1H T channels.

scholarly journals Molecular basis of sidekick-mediated cell-cell adhesion and specificity

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Kerry M Goodman ◽  
Masahito Yamagata ◽  
Xiangshu Jin ◽  
Seetha Mannepalli ◽  
Phinikoula S Katsamba ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Aggregation ◽  
Immunoglobulin Superfamily ◽  
Retinal Neurons ◽  
Isolated Cells ◽  
Recognition Specificity ◽  
Mediate Cell ◽  
Cis And Trans ◽  
Cell Adhesion Proteins ◽  
Cell Cell

Sidekick (Sdk) 1 and 2 are related immunoglobulin superfamily cell adhesion proteins required for appropriate synaptic connections between specific subtypes of retinal neurons. Sdks mediate cell-cell adhesion with homophilic specificity that underlies their neuronal targeting function. Here we report crystal structures of Sdk1 and Sdk2 ectodomain regions, revealing similar homodimers mediated by the four N-terminal immunoglobulin domains (Ig1–4), arranged in a horseshoe conformation. These Ig1–4 horseshoes interact in a novel back-to-back orientation in both homodimers through Ig1:Ig2, Ig1:Ig1 and Ig3:Ig4 interactions. Structure-guided mutagenesis results show that this canonical dimer is required for both Sdk-mediated cell aggregation (via trans interactions) and Sdk clustering in isolated cells (via cis interactions). Sdk1/Sdk2 recognition specificity is encoded across Ig1–4, with Ig1–2 conferring the majority of binding affinity and differential specificity. We suggest that competition between cis and trans interactions provides a novel mechanism to sharpen the specificity of cell-cell interactions.

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