Innervation is essential for the development and differentiation of a sex-specific adult muscle in Drosophila melanogaster

Development ◽  
1995 ◽  
Vol 121 (8) ◽  
pp. 2549-2557 ◽  
Author(s):  
D.A. Currie ◽  
M. Bate

The adult abdominal muscles in Drosophila are generated de novo during metamorphosis and form a simple and characteristic pattern. Throughout adult abdominal development there is a close association between nerves and myoblasts. However, the role of innervation in adult myogenesis is unclear. In males there is an additional muscle, which is unique to abdominal segment 5 (A5). This male specific muscle forms from the same pool of myoblasts as other dorsal muscles in A5 but develops several distinctive characteristics. Previous work indicates the genotype of the innervation of this male specific muscle may play a crucial role in its proper development, although the part played by innervation in the development of other muscles is unknown. Here we test directly the function of innervation in adult myogenesis in general and for the development and differentiation of the male specific muscle in particular. After denervation at the onset of metamorphosis, muscle growth is impaired although the overall muscle pattern continues to develop. Uniquely, the male specific muscle fails to form. Our results indicate that there is an essential role for innervation during the period of metamorphosis for the formation of a full complement of abdominal muscles and for muscle growth. Furthermore, innervation is absolutely required for the formation of the male specific muscle and the development of its special characteristics.

Genetics ◽  
1992 ◽  
Vol 132 (1) ◽  
pp. 179-191
Author(s):  
B J Taylor

Abstract A pair of muscles span the fifth abdominal segment of male but not female Drosophila melanogaster adults. To establish whether genes involved in the development of other sexually dimorphic tissues controlled the differentiation of sex-specific muscles, flies mutant for five known sex-determining genes were examined for the occurrence of male-specific abdominal muscles. Female flies mutant for alleles of Sex-lethal, defective in sex determination, or null alleles of transformer or transformer-2 are converted into phenotypic males that formed male-specific abdominal muscles. Both male and female flies, when mutant for null alleles of doublesex, develop as nearly identical intersexes in other somatic characteristics. Male doublesex flies produced the male-specific muscles, whereas female doublesex flies lacked them. Female flies, even when they inappropriately expressed the male-specific form of doublesex mRNA, failed to produce the male-specific muscles. Therefore, the wild-type products of the genes Sex-lethal, transformer and transformer-2 act to prevent the differentiation of male-specific muscles in female flies. However, there is no role for the genes doublesex or intersex in either the generation of the male-specific muscles in males or their suppression in females.


Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 879-890 ◽  
Author(s):  
D.A. Gailey ◽  
B.J. Taylor ◽  
J.C. Hall

A genetically defined element of the fruitless (fru) locus in Drosophila melanogaster regulates the development of a male-specific muscle spanning the fifth abdominal segment in adult males, the ‘muscle of Lawrence’ (MOL). The region is defined by two cytological deletions, each with a breakpoint that co-maps with previously described mutant courtship phenotypes at cytogenetic interval 91B on the third chromosome. Flies that carry both of these deletions are viable, and males express abnormalities of courtship similar to those caused by the fru inversion breakpoint at 91B. In addition, these double-deletion males show the complete absence of the MOL, suggesting that they have little or no gene expression of a postulated MOL determinant; the musculature in the fifth abdominal segment of these mutants to indistinguishable from that of a normal female. Other mutant combinations that produce fruitless courtship phenotypes—including deletion and inversion breakpoints, and a marked transposon inserted at 91B—produce intermediate forms of the MOL. A new genetic variant, induced by imprecise excision of the marked transposon, is homozygous lethal and disrupts fru functions related to courtship and the MOL. The MOL is shown to be dispensable for fertility and is therefore not the causative factor of fru-induced behavioral sterility. These genetic variants and their phenotypic results are discussed with regard to a model for the organization of the fru locus.


2003 ◽  
Vol 14 (3) ◽  
pp. 939-957 ◽  
Author(s):  
Roger A. Bascom ◽  
Honey Chan ◽  
Richard A. Rachubinski

Pex3p is a peroxisomal integral membrane protein required early in peroxisome biogenesis, and Pex3p-deficient cells lack identifiable peroxisomes. Two temperature-sensitive pex3 mutant strains of the yeast Yarrowia lipolytica were made to investigate the role of Pex3p in the early stages of peroxisome biogenesis. In glucose medium at 16°C, these mutants underwent de novo peroxisome biogenesis and exhibited early matrix protein sequestration into peroxisome-like structures found at the endoplasmic reticulum-rich periphery of cells or sometimes associated with nuclei. The de novo peroxisome biogenesis seemed unsynchronized, with peroxisomes occurring at different stages of development both within cells and between cells. Cells with peripheral nascent peroxisomes and cells with structures morphologically distinct from peroxisomes, such as semi/circular tubular structures that immunostained with antibodies to peroxisomal matrix proteins and to the endoplasmic reticulum-resident protein Kar2p, and that surrounded lipid droplets, were observed during up-regulation of peroxisome biogenesis in cells incubated in oleic acid medium at 16°C. These structures were not detected in wild-type or Pex3p-deficient cells. Their role in peroxisome biogenesis remains unclear. Targeting of peroxisomal matrix proteins to these structures suggests that Pex3p directly or indirectly sequesters components of the peroxisome biogenesis machinery. Such a role is consistent with Pex3p overexpression producing cells with fewer, larger, and clustered peroxisomes.


2001 ◽  
Vol 153 (2) ◽  
pp. 329-338 ◽  
Author(s):  
Valerie Horsley ◽  
Bret B. Friday ◽  
Sarah Matteson ◽  
Kristy Miller Kegley ◽  
Jonathan Gephart ◽  
...  

The nuclear factor of activated T cells (NFAT) family of transcription factors regulates the development and differentiation of several tissue types. Here, we examine the role of NFATC2 in skeletal muscle by analyzing adult NFATC2−/− mice. These mice exhibit reduced muscle size due to a decrease in myofiber cross-sectional area, suggesting that growth is blunted. Muscle growth was examined during regeneration after injury, wherein NFATC2-null myofibers form normally but display impaired growth. The growth defect is intrinsic to muscle cells, since the lack of NFATC2 in primary muscle cultures results in reduced cell size and myonuclear number in myotubes. Retroviral-mediated expression of NFATC2 in the mutant cells rescues this cellular phenotype. Myonuclear number is similarly decreased in NFATC2−/− mice. Taken together, these results implicate a novel role for NFATC2 in skeletal muscle growth. We demonstrate that during growth of multinucleated muscle cells, myoblasts initially fuse to form myotubes with a limited number of nuclei and that subsequent nuclear addition and increases in myotube size are controlled by a molecular pathway regulated by NFATC2.


2016 ◽  
Vol 04 (01) ◽  
pp. 4-10

AbstractImmunosuppression permits graft survival after transplantation and consequently a longer and better life. On the other hand, it increases the risk of infection, for instance with cytomegalovirus (CMV). However, the various available immunosuppressive therapies differ in this regard. One of the first clinical trials using de novo everolimus after kidney transplantation [1] already revealed a considerably lower incidence of CMV infection in the everolimus arms than in the mycophenolate mofetil (MMF) arm. This result was repeatedly confirmed in later studies [2–4]. Everolimus is now considered a substance with antiviral properties. This article is based on the expert meeting “Posttransplant CMV infection and the role of immunosuppression”. The expert panel called for a paradigm shift: In a CMV prevention strategy the targeted selection of the immunosuppressive therapy is also a key element. For patients with elevated risk of CMV, mTOR inhibitor-based immunosuppression is advantageous as it is associated with a significantly lower incidence of CMV events.


2004 ◽  
Vol 52 (Suppl 1) ◽  
pp. S122.6-S123
Author(s):  
M. Garg ◽  
C. Bell ◽  
L. Rogers ◽  
S. Bassilian ◽  
W. N.P. Lee

Author(s):  
Georgia Colleluori ◽  
Jessica Perugini ◽  
Giorgio Barbatelli ◽  
Saverio Cinti

AbstractThe mammary gland (MG) is an exocrine gland present in female mammals responsible for the production and secretion of milk during the process of lactation. It is mainly composed by epithelial cells and adipocytes. Among the features that make the MG unique there are 1) its highly plastic properties displayed during pregnancy, lactation and involution (all steps belonging to the lactation cycle) and 2) its requirement to grow in close association with adipocytes which are absolutely necessary to ensure MG’s proper development at puberty and remodeling during the lactation cycle. Although MG adipocytes play such a critical role for the gland development, most of the studies have focused on its epithelial component only, leaving the role of the neighboring adipocytes largely unexplored. In this review we aim to describe evidences regarding MG’s adipocytes role and properties in physiologic conditions (gland development and lactation cycle), obesity and breast cancer, emphasizing the existing gaps in the literature which deserve further investigation.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Abeer K. Shaalan ◽  
Tathyane H. N. Teshima ◽  
Abigail S. Tucker ◽  
Gordon B. Proctor

AbstractLittle is known about the key molecules that regulate cell division during organogenesis. Here we determine the role of the cell cycle promoter aurora kinase B (AURKB) during development, using embryonic salivary glands (E-SGs) as a model. AURKB is a serine/threonine kinase that regulates key events in mitosis, which makes it an attractive target for tailored anticancer therapy. Many reports have elaborated on the role of AURKB in neoplasia and cancer; however, no previous study has shown its role during organ development. Our previous experiments have highlighted the essential requirement for AURKB during adult exocrine regeneration. To investigate if AURKB is similarly required for progression during embryonic development, we pharmacologically inhibited AURKB in developing submandibular glands (SMGs) at embryonic day (E)13.5 and E16.5, using the highly potent and selective drug Barasertib. Inhibition of AURKB interfered with the expansion of the embryonic buds. Interestingly, this effect on SMG development was also seen when the mature explants (E16.5) were incubated for 24 h with another cell cycle inhibitor Aphidicolin. Barasertib prompted apoptosis, DNA damage and senescence, the markers of which (cleaved caspase 3, γH2AX, SA-βgal and p21, respectively), were predominantly seen in the developing buds. In addition to a reduction in cell cycling and proliferation of the epithelial cells in response to AURKB inhibition, Barasertib treatment led to an excessive generation of reactive oxygen species (ROS) that resulted in downregulation of the acinar differentiation marker Mist1. Importantly, inhibition of ROS was able to rescue this loss of identity, with Mist1 expression maintained despite loss of AURKB. Together, these data identify AURKB as a key molecule in supporting embryonic development and differentiation, while inhibiting senescence-inducing signals during organogenesis.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Feifei Zhang ◽  
Hui Wang ◽  
Jiang Yu ◽  
Xueqing Yao ◽  
Shibin Yang ◽  
...  

AbstractDe novo and acquired resistance, which are mainly mediated by genetic alterations, are barriers to effective routine chemotherapy. However, the mechanisms underlying gastric cancer (GC) resistance to chemotherapy are still unclear. We showed that the long noncoding RNA CRNDE was related to the chemosensitivity of GC in clinical samples and a PDX model. CRNDE was decreased and inhibited autophagy flux in chemoresistant GC cells. CRNDE directly bound to splicing protein SRSF6 to reduce its protein stability and thus regulate alternative splicing (AS) events. We determined that SRSF6 regulated the PICALM exon 14 skip splice variant and triggered a significant S-to-L isoform switch, which contributed to the expression of the long isoform of PICALM (encoding PICALML). Collectively, our findings reveal the key role of CRNDE in autophagy regulation, highlighting the significance of CRNDE as a potential prognostic marker and therapeutic target against chemoresistance in GC.


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