scholarly journals The Mesodermal Expression of rolling stone (rost) Is Essential for Myoblast Fusion in Drosophila and Encodes a Potential Transmembrane Protein

1997 ◽  
Vol 138 (2) ◽  
pp. 337-348 ◽  
Author(s):  
Achim Paululat ◽  
Anette Goubeaud ◽  
Christine Damm ◽  
Stefan Knirr ◽  
Susanne Burchard ◽  
...  
Keyword(s):  
Transmembrane Protein ◽  
Myoblast Fusion ◽  
Fusion Process ◽  
Knock Out ◽  
Visceral Mesoderm ◽  
Homologous Genes ◽  
Rolling Stone ◽  
Embryonic Nervous System ◽  
Drosophila Embryos

In homozygous rolling stone embryos, the fusion of myoblasts to syncytial myotubes is diminished. Nevertheless, the visceral mesoderm, the heart mesoderm, and few somatic muscles are properly formed. Thus, we postulate a central role of rolling stone for the fusion process within the somatic mesoderm. We have cloned the rolling stone gene, and the deduced protein sequence is in accordance with a transmembrane protein, which agrees with the enrichment of Rost in the membrane fraction of Drosophila embryos. No homologous genes have been described so far. rolling stone is expressed in the embryonic nervous system and cells of the somatic mesoderm, most notable in muscle founder cells. To elucidate the function of rolling stone for myoblast fusion, we applied a knock-out strategy. The expression of an antisense rolling stone transcript specifically within the mesoderm of wild-type embryos results in fusion defects of myoblasts, proving that the rolling stone expression in the mesoderm is responsible for the rolling stone phenotype. We suggest that rolling stone is a member of a group of genes that are necessary for the fusion process during myogenesis.

Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3163-3174 ◽  
Author(s):  
D.J. Roberts ◽  
R.L. Johnson ◽  
A.C. Burke ◽  
C.E. Nelson ◽  
B.A. Morgan ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Target Genes ◽  
Hox Genes ◽  
Ectopic Expression ◽  
Secreted Protein ◽  
Gut Development ◽  
Visceral Mesoderm ◽  
Homologous Genes ◽  
Inductive Signal

Reciprocal inductive signals between the endoderm and mesoderm are critical to vertebrate gut development. Sonic hedgehog encodes a secreted protein known to act as an inductive signal in several regions of the developing embryo. In this report, we provide evidence to support the role of Sonic hedgehog and its target genes Bmp-4 and the Abd-B-related Hox genes in the induction and patterning the chick hindgut. Sonic is expressed in the definitive endoderm at the earliest stage of chick gut formation. Immediately subjacent to Sonic expression in the caudal endoderm is undifferentiated mesoderm, later to become the visceral mesoderm of the hindgut. Genes expressed within this tissue include Bmp-4 (a TGF-beta relative implicated in proper growth of visceral mesoderm) and members of the Abd-B class of Hox genes (known regulators of pattern in many aspects of development). Using virally mediated misexpression, we show that Sonic hedgehog is sufficient to induce ectopic expression of Bmp-4 and specific Hoxd genes within the mesoderm. Sonic therefore appears to act as a signal in an epithelial-mesenchymal interaction in the earliest stages of chick hindgut formation. Gut pattern is evidenced later in gut morphogenesis with the presence of anatomic boundaries reflecting phenotypically and physiologically distinct regions. The expression pattern of the Abd-b-like Hox genes remains restricted in the hindgut and these Hox expression domains reflect gut morphologic boundaries. This finding strongly supports a role for these genes in determining the adult gut phenotype. Our results provide the basis for a model to describe molecular controls of early vertebrate hindgut development and patterning. Expression of homologous genes in Drosophila suggest that aspects of gut morphogenesis may be regulated by similar inductive networks in the two organisms.

scholarly journals Fusogenic micropeptide Myomixer is essential for satellite cell fusion and muscle regeneration

2018 ◽  
Vol 115 (15) ◽  
pp. 3864-3869 ◽  
Author(s):  
Pengpeng Bi ◽  
John R. McAnally ◽  
John M. Shelton ◽  
Efrain Sánchez-Ortiz ◽  
Rhonda Bassel-Duby ◽  
...  
Keyword(s):  
Satellite Cell ◽  
Cell Fusion ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Transmembrane Protein ◽  
Myoblast Fusion ◽  
Conditional Knockout ◽  
Genetic Deletion ◽  
Specific Membrane

Regeneration of skeletal muscle in response to injury occurs through fusion of a population of stem cells, known as satellite cells, with injured myofibers. Myomixer, a muscle-specific membrane micropeptide, cooperates with the transmembrane protein Myomaker to regulate embryonic myoblast fusion and muscle formation. To investigate the role of Myomixer in muscle regeneration, we used CRISPR/Cas9-mediated genome editing to generate conditional knockout Myomixer alleles in mice. We show that genetic deletion of Myomixer in satellite cells using a tamoxifen-regulated Cre recombinase transgene under control of the Pax7 promoter abolishes satellite cell fusion and prevents muscle regeneration, resulting in severe muscle degeneration after injury. Satellite cells devoid of Myomixer maintain expression of Myomaker, demonstrating that Myomaker alone is insufficient to drive myoblast fusion. These findings, together with prior studies demonstrating the essentiality of Myomaker for muscle regeneration, highlight the obligatory partnership of Myomixer and Myomaker for myofiber formation throughout embryogenesis and adulthood.

scholarly journals Loss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xin Ding ◽  
Jin Wang ◽  
Miaoxin Huang ◽  
Zhangpeng Chen ◽  
Jing Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Knock Out ◽  
Classical Complement Pathway ◽  
Synaptic Remodeling ◽  
The Central Nervous System ◽  
System Activation ◽  
Knock Out Mice ◽  
Synaptic Pruning

AbstractMicroglia play a key role in regulating synaptic remodeling in the central nervous system. Activation of classical complement pathway promotes microglia-mediated synaptic pruning during development and disease. CD47 protects synapses from excessive pruning during development, implicating microglial SIRPα, a CD47 receptor, in synaptic remodeling. However, the role of microglial SIRPα in synaptic pruning in disease remains unclear. Here, using conditional knock-out mice, we show that microglia-specific deletion of SIRPα results in decreased synaptic density. In human tissue, we observe that microglial SIRPα expression declines alongside the progression of Alzheimer’s disease. To investigate the role of SIRPα in neurodegeneration, we modulate the expression of microglial SIRPα in mouse models of Alzheimer’s disease. Loss of microglial SIRPα results in increased synaptic loss mediated by microglia engulfment and enhanced cognitive impairment. Together, these results suggest that microglial SIRPα regulates synaptic pruning in neurodegeneration.

scholarly journals Knock out of tmem38b by CRISPR/Cas9 in zebrafish unveils the in vivo role of Trimeric intracellular cation (TRIC) channel B on cell homeostasis

Bone Reports ◽  
2021 ◽  
Vol 14 ◽  
pp. 101054
Author(s):  
Laura Leoni ◽  
Valentina Daponte ◽  
Francesca Tonelli ◽  
Roberta Gioia ◽  
Silvia Cotti ◽  
...  
Keyword(s):  
Cell Homeostasis ◽  
Knock Out

scholarly journals Role of laser powder bed fusion process parameters in crystallographic texture of additive manufactured Nb-48Ti alloy

2021 ◽  
Author(s):  
Rafael de Moura Nobre ◽  
Willy Ank de Morais ◽  
Matheus Tavares Vasques ◽  
Jhoan Guzmán ◽  
Daniel Luiz Rodrigues Junior ◽  
...  
Keyword(s):  
Process Parameters ◽  
Crystallographic Texture ◽  
Fusion Process ◽  
Powder Bed Fusion ◽  
Laser Powder Bed Fusion ◽  
Powder Bed

scholarly journals Prediction of Functional Consequences of Missense Mutations in ANO4 Gene

2021 ◽  
Vol 22 (5) ◽  
pp. 2732
Author(s):  
Nadine Reichhart ◽  
Vladimir M. Milenkovic ◽  
Christian H. Wetzel ◽  
Olaf Strauß
Keyword(s):  
Transmembrane Protein ◽  
Functional Characterization ◽  
Missense Mutations ◽  
Mutant Proteins ◽  
Functional Consequences ◽  
New Perspective ◽  
The Stability ◽  
Dynamics Simulations ◽  
And Function

The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca2+-dependent ion channels and/or Ca2+-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4.

scholarly journals The Extracellular Small Leucine-Rich Proteoglycan Biglycan Is a Key Player in Gastric Cancer Aggressiveness

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1330
Author(s):  
Filipe Pinto ◽  
Liliana Santos-Ferreira ◽  
Marta T. Pinto ◽  
Catarina Gomes ◽  
Celso A. Reis
Keyword(s):  
Clinical Value ◽  
Knock Out ◽  
Angiogenic Potential ◽  
In Vivo Experiments ◽  
Cancer Aggressiveness ◽  
Advanced Stages ◽  
Oncogenic Gene

Biglycan (BGN gene), an extracellular proteoglycan, has been described to be associated with cancer aggressiveness. The purpose of this study was to clarify the clinical value of biglycan as a biomarker in multiple independent GC cohorts and determine the in vitro and in vivo role of biglycan in GC malignant features. We found that BGN is commonly over-expressed in all analyzed cohorts, being associated with disease relapse and poor prognosis in patients with advanced stages of disease. In vitro and in vivo experiments demonstrated that biglycan knock-out GC cells display major phenotypic changes with a lower cell survival, migration, and angiogenic potential when compared with biglycan expressing cells. Biglycan KO GC cells present increased levels of PARP1 and caspase-3 cleavage and a decreased expression of mesenchymal markers. Importantly, biglycan deficient GC cells that were supplemented with exogenous biglycan were able to restore biological features, such as survival, clonogenic and migratory capacities. Our in vitro and in vivo findings were validated in human GC samples, where BGN expression was associated with several oncogenic gene signatures that were associated with apoptosis, cell migration, invasion, and angiogenesis. This study provided new insights on biglycan role in GC that should be taken in consideration as a key cellular regulator with major impact in tumor progression and patients’ clinical outcome.

scholarly journals A Potential Compensatory Role of Panx3 in the VNO of a Panx1 Knock Out Mouse Model

2018 ◽  
Vol 11 ◽  
Author(s):  
Paige Whyte-Fagundes ◽  
Stefan Kurtenbach ◽  
Christiane Zoidl ◽  
Valery I. Shestopalov ◽  
Peter L. Carlen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Knock Out ◽  
Knock Out Mouse

The Role of Serotonin in the Development of Psychiatric Disorders: Studies on Drug Dependence and Anxiety-like Behaviour Following the Genetic Reduction of the Serotonin Transporter

2021 ◽  
Author(s):  
◽  
Alana Oakly
Keyword(s):  
Psychiatric Disorders ◽  
Early Development ◽  
Drug Dependence ◽  
Primary Objective ◽  
Behavioural Response ◽  
Mrna Levels ◽  
Self Administration ◽  
Knock Out ◽  
Enhanced Sensitivity

<p>Rationale: Given the high prevalence and large burden of psychiatric disorders it is imperative to determine the underling etiology in order for better understanding and treatment. The neurotransmitter serotonin (5-HT) has been associated with mental disorders in humans both pharmacologically and genetically. Individuals with the short-allele of a prominent polymorphism within the 5-HT transporter (SERT) show increased incidence of mood disorders and drug dependence. However, whether or not dysregulation in the 5-HT system causes, or is just associated with, psychiatric disorders is impossible to determine from human studies alone. Consequently, it is imperative to employ an animal model of down-regulated SERT function. To better understand the role of 5-HT in drug dependence, the rat’s behavioural response to the psychostimulant (±) 3, 4-methylenedioxymethamphetamine (MDMA), a preferentially serotonergically mediated drug, was assessed. Finally, the ability to rescue the anxiety-like phenotype in the SERT-/- rat by altering extracellular 5-HT during early development was also evaluated.  Objective: The primary objective of the current thesis was to determine whether dysregulation of 5-HT is directly linked to the occurrence of psychiatric disorders, particularly drug dependence and anxiety.  Methods: A model of down-regulated SERT function, the SERT knock-out (SERT-/-) rat, was used for all experiments in order to determine a causal relationship between 5-HT dysregulation and psychiatric disorders. In Chapter 2, the response of the SERT-/- rats to various tasks usually disrupted by MDMA was assessed. In Chapter 3, the sensitivity of the SERT-/- rats to the reinforcing effects of MDMA was determined using the self-administration paradigm. Finally, in Chapter 4, whether the anxiety-like behaviour of the SERT-/- rat could be rescued through normalising excessive extracellular 5-HT neonatally was assessed. An attempt was also made to determine a mechanism by which 5-HT dysregulation could alter behaviour. To this end, gene expression previously found to be up- or down-regulated in the SERT-/- rat was assessed in the neonatally treated rats.  Results: The results of Chapter 2 indicated the SERT is necessary for MDMA’s disruption of startle habituation but not its psychomotor effects. Moreover, for those rats that could discriminate low dose MDMA from saline, genetic removal of the SERT resulted in the inability to discriminate MDMA from amphetamine, implying that, in these rats, MDMA was now subjectively indistinguishable from amphetamine. Indeed, this alteration also resulted in enhanced sensitivity to the reinforcing properties of MDMA, giving MDMA the qualities of a traditional psychostimulant in SERT-/- rats (Chapter 3). Finally, lowering the excessive 5-HT during neonatal development in SERT-/- rats led to a rescue of mild, but not high, anxiety-like behaviour in males. However, mRNA levels of long 3’NTR BDNF and 5-HT1a, genes associated with neurodevelopment, remained unchanged across genotypes and treatment groups (Chapter 4).  Conclusions: Genetic removal of the 5-HT transporter results in an altered behavioural response to MDMA, in particular an increased sensitivity to its reinforcing properties. However, while the genetic removal of the SERT results in enhanced extracellular 5-HT, the pathological phenotypes present in this rat are likely due to this increase occurring in early development, not its continued presence in adulthood. Overall, these findings contribute to the growing body of literature indicating that enhanced brain 5-HT during early development can lead to pathological behaviour in adulthood.</p>

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