Search results for "drosophila"
showing 10 items of 782 documents
Dpp signaling inhibits proliferation in the Drosophila wing by Omb-dependent regional control of bantam
2013
The control of organ growth is a fundamental aspect of animal development but remains poorly understood. The morphogen Dpp has long been considered as a general promoter of cell proliferation during Drosophila wing development. It is an ongoing debate whether the Dpp gradient is required for the uniform cell proliferation observed in the wing imaginal disc. Here, we investigated how the Dpp signaling pathway regulates proliferation during wing development. By systematic manipulation of Dpp signaling we observed that it controls proliferation in a region-specific manner: Dpp, via omb, promoted proliferation in the lateral and repressed proliferation in the medial wing disc. Omb controlled th…
Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC.
1994
We have analysed 118 families with inherited medullary thyroid carcinoma (MTC) for mutations of the RET proto-oncogene. These included cases of multiple endocrine neoplasia types 2A (MEN 2A) and 2B (MEN 2B) and familial MTC (FMTC). Mutations at one of 5 cysteines in the extracellular domain were found in 97% of patients with MEN 2A and 86% with FMTC but not in MEN 2B patients or normal controls. 84% of the MEN2A mutations affected codon 634. MEN 2A patients with a Cys634 to Arg substitution had a greater risk of developing parathyroid disease than those with other codon 634 mutations. Our data show a strong correlation between disease phenotype and the nature and position of the RET mutatio…
Software/Hardware Issues in Modelling Insect Brain Architecture
2011
The concept of cognitive abilities is commonly associated to humans and animals like mammals, birds and others. Nevertheless, in the last years several research groups have intensified the studies on insects that posses a much simpler brain structure even if they are able to show interesting memory and learning capabilities. In this paper a survey on some key results obtained in a joint research activity among Engineers and Neurogeneticians is reported. They were focussed toward the design and implementation of a model of the insect brain inspired by the Drosophila melanogaster. Particular attention was paid to the main neural centers the Mushroom Bodies and the Central Complex. Moreover a …
Regulación transcripcional de muscleblind y nuevos mecanismos de patogénesis en un modelo de distrofia miotónica en Drosophila
2015
La distrofia miotónica tipo I es una enfermedad genética con un patrón de herencia autosómico dominante. Se considera una enfermedad rara ya que afecta a 1 de cada 8000 personas, sin embargo, es la forma más común de distrofia en adultos. Es una enfermedad multisistémica que se caracteriza por la aparición de cataratas iridiscenctes, defectos en la conducción cardíaca, miotonía y atrofia muscular. Sin embargo, hasta la fecha no existen tratamientos efectivos. La enfermedad se produce por la expansión del triplete CTG en la región 3¿ no traducida del gen DMPK. Las expansiones forman unas horquillas de RNA capaces de secuestrar diversas proteínas de unión a RNA, entre ellas, el factor de spli…
Descubrimiento y caracterización de la estefenantrina como fármaco para la Distrofia Miotónica Tipo 1
2015
La Distrofia Miotónica tipo 1 (DM1) es una enfermedad autosómica dominante cuyos principales síntomas incluyen miotonía (incapacidad para relajar el músculo tras una contracción voluntaria), degeneración muscular, cataratas, diabetes, arritmias cardiacas y déficit cognitivo entre otros. La causa genética de la enfermedad radica en la expansión del trinucleótido CTG en el extremo 3’ no traducido del gen proteina kinasa de la distrofia miotónica (DMPK). La expansión de este trinucleótido provoca la ganancia de función tóxica del RNA al transcribirse la región expandida. El RNA portador de las expansiones tóxicas de CTG se pliega sobre sí mismo formando una horquilla de doble cadena que queda …
Derepressing muscleblind expression by miRNA sponges ameliorates myotonic dystrophy-like phenotypes in Drosophila
2016
AbstractMyotonic Dystrophy type 1 (DM1) originates from alleles of the DMPK gene with hundreds of extra CTG repeats in the 3′ untranslated region (3′ UTR). CUG repeat RNAs accumulate in foci that sequester Muscleblind-like (MBNL) proteins away from their functional target transcripts. Endogenous upregulation of MBNL proteins is, thus, a potential therapeutic approach to DM1. Here we identify two miRNAs, dme-miR-277 and dme-miR-304, that differentially regulate muscleblind RNA isoforms in miRNA sensor constructs. We also show that their sequestration by sponge constructs derepresses endogenous muscleblind not only in a wild type background but also in a DM1 Drosophila model expressing non-co…
Expanded CCUG repeat RNA expression in Drosophila heart and muscle trigger Myotonic Dystrophy type 1-like phenotypes and activate autophagocytosis ge…
2016
AbstractMyotonic dystrophies (DM1–2) are neuromuscular genetic disorders caused by the pathological expansion of untranslated microsatellites. DM1 and DM2, are caused by expanded CTG repeats in the 3′UTR of the DMPK gene and CCTG repeats in the first intron of the CNBP gene, respectively. Mutant RNAs containing expanded repeats are retained in the cell nucleus, where they sequester nuclear factors and cause alterations in RNA metabolism. However, for unknown reasons, DM1 is more severe than DM2. To study the differences and similarities in the pathogenesis of DM1 and DM2, we generated model flies by expressing pure expanded CUG ([250]×) or CCUG ([1100]×) repeats, respectively, and compared …
Muscleblind, BSF and TBPH are mislocalized in the muscle sarcomere of a Drosophila myotonic dystrophy model
2012
SummaryMyotonic dystrophy type 1 (DM1) is a genetic disease caused by the pathological expansion of a CTG trinucleotide repeat in the 3' UTR of the DMPK gene. In the DMPK transcripts, the CUG expansions sequester RNA-binding proteins into nuclear foci, including transcription factors and alternative splicing regulators such as MBNL1. MBNL1 sequestration has been associated with key features of DM1. However, the basis behind a number of molecular and histological alterations in DM1 remain unclear. To help identify new pathogenic components of the disease, we carried out a genetic screen using a Drosophila model of DM1 that expresses 480 interrupted CTG repeats, i(CTG)480, and a collection of…
Modeling of Myotonic Dystrophy Cardiac Phenotypes in
2018
After respiratory distress, cardiac dysfunction is the second most common cause of fatality associated with the myotonic dystrophy (DM) disease. Despite the prevalance of heart failure in DM, physiopathological studies on heart symptoms have been relatively scarce because few murine models faithfully reproduce the cardiac disease. Consequently, only a small number of candidate compounds have been evaluated in this specific phenotype. To help cover this gap Drosophila combines the amenability of its invertebrate genetics with the possibility of quickly acquiring physiological parameters suitable for meaningful comparisons with vertebrate animal models and humans. Here we review available des…
Papel del complejo de proteínas Rab-Rabphilin en un modelo de daño renal en Drosophila
2019
La enfermedad renal crónica (ERC) es una de las enfermedades más prevalentes en la actualidad, con un 10 % de personas que la sufren en todo el mundo. La aparición de la enfermedad puede deberse a diferentes causas como la diabetes, hipertensión, estado del sistema inmune y genéticas, siendo la hiperglucemia una de las más comunes y responsable de la mayoría de los casos. Esto convierte a la nefropatía diabética en la causa más frecuente de enfermedad renal en etapa terminal (ESRD) en la mayoría de los países. La ERC es progresiva y el tratamiento sólo logra enlentecer su progresión, pero no revertirla. De ahí la necesidad de identificar mecanismos implicados en el daño renal y de encontrar…