Mechanisms of Development最新文献

{"title":"Notch signaling in the division of germ layers in bilaterian embryos","authors":"María Belén Favarolo,&nbsp;Silvia L. López","doi":"10.1016/j.mod.2018.06.005","DOIUrl":"10.1016/j.mod.2018.06.005","url":null,"abstract":"<div><p>Bilaterian embryos are triploblastic organisms which develop three complete germ layers (ectoderm, mesoderm, and endoderm). While the ectoderm develops mainly from the animal hemisphere, there is diversity in the location from where the endoderm and the mesoderm arise in relation to the animal-vegetal axis, ranging from endoderm being specified between the ectoderm and mesoderm in echinoderms, and the mesoderm being specified between the ectoderm and the endoderm in vertebrates. A common feature is that part of the mesoderm segregates from an ancient bipotential endomesodermal domain. The process of segregation is noisy during the initial steps but it is gradually refined. In this review, we discuss the role of the Notch pathway in the establishment and refinement of boundaries between germ layers in bilaterians, with special focus on its interaction with the Wnt/β-catenin pathway.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"154 ","pages":"Pages 122-144"},"PeriodicalIF":2.6,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2018.06.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36255828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone regeneration after traumatic skull injury in Xenopus tropicalis","authors":"David Muñoz ,&nbsp;Héctor Castillo ,&nbsp;Juan Pablo Henríquez ,&nbsp;Sylvain Marcellini","doi":"10.1016/j.mod.2018.06.007","DOIUrl":"10.1016/j.mod.2018.06.007","url":null,"abstract":"<div><p>The main purpose of regenerative biology is to improve human health by exploiting cellular and molecular mechanisms favoring tissue repair. In recent years, non-mammalian vertebrates have emerged as powerful model organisms to tackle the problem of tissue regeneration. Here, we analyze the process of bone repair in metamorphosing <em>Xenopus tropicalis</em> tadpoles subjected to traumatic skull injury. Five days after skull perforation, a dense and highly vascularized mesenchymal is apparent over the injury site. Using an <em>in vivo</em> bone staining procedure based on independent pulses of Alizarin red and Calcein green, we show that the deposition of new bone matrix completely closes the wound in 15 days. The absence of cartilage implies that bone repair follows an intramembranous ossification route. Collagen second harmonic imaging reveals that while a well-organized lamellar type of bone is deposited during development, a woven type of bone is produced during the early-phase of the regeneration process. Osteoblasts lying against the regenerating bone robustly express fibrillar <em>collagen 1a1</em>, <em>SPARC</em> and <em>Dlx5</em>. These analyses establish <em>Xenopus tropicalis</em> as a new model system to improve traumatic skull injury recovery.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"154 ","pages":"Pages 153-161"},"PeriodicalIF":2.6,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2018.06.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36717457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in vitro method for studying subcellular rearrangements during cell polarization in Drosophila melanogaster hemocytes","authors":"Sandra Sofía Edwards ,&nbsp;María Graciela Delgado ,&nbsp;Guilherme Pedreira de Freitas Nader ,&nbsp;Matthieu Piel ,&nbsp;Yohanns Bellaïche ,&nbsp;Ana María Lennon-Duménil ,&nbsp;Álvaro Glavic","doi":"10.1016/j.mod.2018.08.003","DOIUrl":"10.1016/j.mod.2018.08.003","url":null,"abstract":"<div><p>Thanks to the power of <em>Drosophila</em> genetics, this animal model has been a precious tool for scientists to uncover key processes associated to innate immunity. The fly immune system relies on a population of macrophage-like cells, also referred to as hemocytes, which are highly migratory and phagocytic, and can easily be followed <em>in vivo.</em> These cells have shown to play important roles in fly development, both at the embryonic and pupal stages. However, there is no robust assay for the study of hemocyte migration <em>in vitro</em>, which limits our understanding of the molecular mechanisms involved. Here, we contribute to fill this gap by showing that hemocytes adopt a polarized morphology upon ecdysone stimulation, allowing the study of the cytoskeleton rearrangements and organelle reorganization that take place during the first step of cell locomotion.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"154 ","pages":"Pages 277-286"},"PeriodicalIF":2.6,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2018.08.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36387689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of stress-related muscle atrophy in fish: An ex vivo approach","authors":"Julia Torres-Velarde ,&nbsp;Raúl Llera-Herrera ,&nbsp;Teresa García-Gasca ,&nbsp;Alejandra García-Gasca","doi":"10.1016/j.mod.2018.07.002","DOIUrl":"10.1016/j.mod.2018.07.002","url":null,"abstract":"<div><p>Muscle development involves coordinated molecular events leading to cell proliferation, fusion, differentiation, sarcomere assembly, and myofibrogenesis. However, under physiological or pathological stress, energy requirements and secretion of glucocorticoids increase, resulting in muscle atrophy because of the depletion of energy reserves. Glucocorticoids induce muscular atrophy by two main mechanisms, protein degradation through the ubiquitin-proteasome system, and inhibition of protein synthesis through the negative regulation of the IGF1-Akt-mTOR signaling pathway. Other signaling pathways (such as the myostatin-activin-smad pathway) involved in muscle atrophy by glucocorticoid exposure are unclear. In fish, the role of glucocorticoids in muscle atrophy has not been fully elucidated. The aim of the present study was to evaluate the mechanisms of muscle atrophy induced by a synthetic glucocorticoid (dexamethasone, DEX) in an <em>ex vivo</em> muscle culture system of a marine fish (<em>Lutjanus guttatus</em>). Results showed that DEX was able to induce the expression of <em>myostatin-1</em>, and the expression of the transcription factor <em>foxo3b</em>. <em>Myostatin-1</em> silencing by RNAi produced a decrease in the expression of <em>foxo3b</em> and <em>murf1</em>, and increased the expression of <em>mtor</em>, <em>myod-2</em> and <em>myogenin</em>. These results suggest that in fish skeletal muscle, myostatin-1 signaling participates in glucocorticoid-induced muscle wasting through the negative regulation of genes involved in muscle growth, such as <em>mtor</em>, <em>myod-2</em> and <em>myogenin</em>, and the induction of atrophy genes like <em>foxo3b</em> and <em>murf1</em>.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"154 ","pages":"Pages 162-169"},"PeriodicalIF":2.6,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2018.07.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36291468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation and function of p53: A perspective from Drosophila studies","authors":"María Clara Ingaramo ,&nbsp;Juan A. Sánchez ,&nbsp;Andrés Dekanty","doi":"10.1016/j.mod.2018.05.007","DOIUrl":"10.1016/j.mod.2018.05.007","url":null,"abstract":"<div><p><em>Tp53</em> is a central regulator of cellular responses to stress and one of the most frequently mutated genes in human cancers. P53 is activated by a myriad of stress signals and drives specific cellular responses depending on stress nature, cell type and cellular context. Additionally to its classical functions in regulating cell cycle arrest, apoptosis and senescence, newly described non-canonical functions of p53 are increasingly coming under the spotlight as important functions not only for its role as a tumour suppressor but also for its non-cancer associated activities. <em>Drosophila melanogaster</em> is a valuable model to study multiple aspects of normal animal physiology, stress response and disease. In this review, we discuss the contribution of <em>Drosophila</em> studies to the current knowledge on p53 and highlight recent evidences pointing to p53 novel roles in promoting tissue homeostasis and metabolic adaptation.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"154 ","pages":"Pages 82-90"},"PeriodicalIF":2.6,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2018.05.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36131741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jitterbug/Filamin and Myosin-II form a complex in tendon cells required to maintain epithelial shape and polarity during musculoskeletal system development","authors":"Catalina Manieu ,&nbsp;Gonzalo H. Olivares ,&nbsp;Franco Vega-Macaya,&nbsp;Mauricio Valdivia,&nbsp;Patricio Olguín","doi":"10.1016/j.mod.2018.09.002","DOIUrl":"10.1016/j.mod.2018.09.002","url":null,"abstract":"<div><p>During musculoskeletal system development, mechanical tension is generated between muscles and tendon-cells. This tension is required for muscle differentiation and is counterbalanced by tendon-cells avoiding tissue deformation. Both, Jbug/Filamin, an actin-meshwork organizing protein, and non-muscle Myosin-II (Myo-II) are required to maintain the shape and cell orientation of the <em>Drosophila</em> notum epithelium during flight muscle attachment to tendon cells.</p><p>Here we show that halving the genetic dose of Rho kinase (Drok), the main activator of Myosin-II, enhances the epithelial deformation and bristle orientation defects associated with <em>jbug/Filamin</em> knockdown. Drok and activated Myo-II localize at the apical cell junctions, tendon processes and are associated to the myotendinous junction. Further, we found that Jbug/Filamin co-distribute at tendon cells with activated Myo-II. Finally, we found that Jbug/Filamin and Myo-II are in the same molecular complex and that the actin-binding domain of Jbug/Filamin is necessary for this interaction.</p><p>These data together suggest that Jbug/Filamin and Myo-II proteins may act together in tendon cells to balance the tension generated during development of muscles-tendon interaction, maintaining the shape and polarity of the <em>Drosophila</em> notum epithelium.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"154 ","pages":"Pages 309-314"},"PeriodicalIF":2.6,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2018.09.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36489499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The biology and evolution of the Dilp8-Lgr3 pathway: A relaxin-like pathway coupling tissue growth and developmental timing control","authors":"Alisson M. Gontijo ,&nbsp;Andres Garelli","doi":"10.1016/j.mod.2018.04.005","DOIUrl":"10.1016/j.mod.2018.04.005","url":null,"abstract":"<div><p>Many insects, like cockroaches, moths, and flies, can regenerate tissues by extending the growth-competent phases of their life cycle. The molecular and cellular players mediating this coordination between tissue growth and developmental timing have been recently discovered in <em>Drosophila</em>. The insulin/relaxin-like peptide, Dilp8, was identified as a factor communicating abnormal growth status of <em>Drosophila</em> larval imaginal discs to the neuroendocrine centers that control the timing of the onset of metamorphosis. Dilp8 requires a neuronal relaxin receptor for this function, the Leucine rich repeat containing G protein coupled receptor, Lgr3. A review of current data supports a model where imaginal disc-derived Dilp8 acts on four central nervous system Lgr3-positive neurons to activate cyclic-AMP signaling in an Lgr3-dependent manner. This causes a reduction in ecdysone hormone production by the larval endocrine prothoracic gland, which leads to a delay in the onset of metamorphosis and a simultaneous slowing down in the growth rates of healthy imaginal tissues, promoting the generation of proportionate individuals. We discuss reports indicating that the Dilp8-Lgr3 pathway might have other functions at different life history stages, which remain to be elucidated, and review molecular evolution data on invertebrate genes related to the relaxin-pathway. The strong conservation of the relaxin pathway throughout animal evolution contrasts with instances of its complete loss in some clades, such as lepidopterans, which must coordinate growth and developmental timing using another mechanism. Research into these areas should generate exciting new insights into the biology of growth coordination, the evolution of the relaxin signaling pathway, and likely reveal unforeseen functions in other developmental stages.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"154 ","pages":"Pages 44-50"},"PeriodicalIF":2.6,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2018.04.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36059707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A role for Lin-28 in growth and metamorphosis in Drosophila melanogaster","authors":"Sergio González-Itier ,&nbsp;Esteban G. Contreras ,&nbsp;Juan Larraín ,&nbsp;Álvaro Glavic ,&nbsp;Fernando Faunes","doi":"10.1016/j.mod.2018.06.002","DOIUrl":"10.1016/j.mod.2018.06.002","url":null,"abstract":"<div><p>Insect metamorphosis has been a classic model to understand the role of hormones in growth and timing of developmental transitions. In addition to hormones, transitions in some species are regulated by genetic programs, such as the heterochronic gene network discovered in <em>C</em>. <em>elegans</em>. However, the functional link between hormones and heterochronic genes is not clear. The heterochronic gene <em>lin</em>-<em>28</em> is involved in the maintenance of stem cells, growth and developmental timing in vertebrates. In this work, we used <em>gain</em>-<em>of</em>-<em>function</em> and <em>loss</em>-<em>of</em>-<em>function</em> experiments to study the role of Lin-28 in larval growth and the timing of metamorphosis of <em>Drosophila melanogaster</em>. During the late third instar stage, Lin-28 is mainly expressed in neurons of the central nervous system and in the intestine. <em>Loss</em>-<em>of</em>-<em>function lin</em>-<em>28</em> mutant larvae are smaller and the larval-to-pupal transition is accelerated. This faster transition correlates with increased levels of ecdysone direct target genes such as <em>Broad</em>-<em>Complex</em> (<em>BR</em>-<em>C</em>) and <em>Ecdysone Receptor</em> (<em>EcR</em>). Overexpression of Lin-28 does not affect the timing of pupariation but most animals are not able to eclose, suggesting defects in metamorphosis. Overexpression of human Lin-28 results in delayed pupariation and the death of animals during metamorphosis. Altogether, these results suggest that Lin-28 is involved in the control of growth during larval development and in the timing and progression of metamorphosis.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"154 ","pages":"Pages 107-115"},"PeriodicalIF":2.6,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2018.06.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36227854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fos metamorphoses: Lessons from mutants in model organisms","authors":"Carlos Alfonso-Gonzalez ,&nbsp;Juan Rafael Riesgo-Escovar","doi":"10.1016/j.mod.2018.05.006","DOIUrl":"10.1016/j.mod.2018.05.006","url":null,"abstract":"<div><p>The Fos oncogene gene family is evolutionarily conserved throughout Eukarya. Fos proteins characteristically have a leucine zipper and a basic region with a helix-turn-helix motif that binds DNA. In vertebrates, there are several Fos homologs. They can homo- or hetero-dimerize via the leucine zipper domain. Fos homologs coupled with other transcription factors, like Jun oncoproteins, constitute the Activator Protein 1 (AP-1) complex. From its original inception as an oncogene, the subsequent finding that they act as transcription factors binding DNA sequences known as TRE, to the realization that they are activated in many different scenarios, and to loss-of-function analysis, the Fos proteins have traversed a multifarious path in development and physiology. They are instrumental in ‘immediate early genes’ responses, and activated by a seemingly myriad assemblage of different stimuli. Yet, the majority of these studies were basically gain-of-function studies, since it was thought that Fos genes would be cell lethal. Loss-of-function mutations in vertebrates were recovered later, and were not cell lethal. In fact, <em>c-fos</em> null mutations are viable with developmental defects (osteopetrosis and myeloid lineage abnormalities). It was then hypothesized that vertebrate genomes exhibit partial redundancy, explaining the ‘mild’ phenotypes, and complicating assessment of complete loss-of-function phenotypes. Due to its promiscuous activation, <em>fos</em> genes (especially <em>c-fos</em>) are now commonly used as markers for cellular responses to stimuli. <em>fos</em> homologs high sequence conservation (including <em>Drosophila</em>) is advantageous as it allows critical assessment of <em>fos</em> genes functions in this genetic model. <em>Drosophila melanogaster</em> contains only one <em>fos</em> homolog, the gene <em>kayak</em>. <em>kayak</em> mutations are lethal, and allow study of all the processes where <em>fos</em> is required. The <em>kayak</em> locus encodes several different isoforms, and is a pleiotropic gene variously required for development involving cell shape changes. In general, <em>fos</em> genes seem to primarily activate programs involved in cellular architectural rearrangements and cell shape changes.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"154 ","pages":"Pages 73-81"},"PeriodicalIF":2.6,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2018.05.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36092717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial permeability transition pore in sea urchin female gametes","authors":"Elis Torrezan-Nitao ,&nbsp;Regina Celia Bressan Queiroz Figueiredo ,&nbsp;Luis Fernando Marques-Santos","doi":"10.1016/j.mod.2018.07.008","DOIUrl":"10.1016/j.mod.2018.07.008","url":null,"abstract":"<div><p>Mitochondrial permeability transition pore (MPTP) has been associated to calcium homeostasis and reactive oxygen species (ROS) generation in several cell types. While extensively investigated in somatic cells, there are few data regarding MPTP phenomenon in gametes. The aim of the present work was to investigate MPTP occurrence in sea urchin female gametes. The protonophores CCCP and FCCP, and the Ca²⁺ ionophore ionomycin, were used as pore inductors. Pore opening was monitored by mitochondrial potential sensitive probes and cobalt-quenched calcein assay. The pore desensitizer cyclosporin A (CsA) prevented the loss of mitochondrial inner membrane potential (ΔΨ_m) and pore opening induced by MPTP activators. The disruption of ΔΨ_m led to an increase in ROS generation, which was completely prevented by CsA. Our data also demonstrated that the increase in ROS production induced by MPTP opening requires extracellular Ca²⁺. In summary, the current study provides evidence about the occurrence of MPTP in sea urchin eggs in a similar manner as described in vertebrate somatic cells - CsA-sensitive, voltage- and Ca²⁺-triggered - and shows MPTP as a highly conserved physiological event through the evolution.</p></div>","PeriodicalId":49844,"journal":{"name":"Mechanisms of Development","volume":"154 ","pages":"Pages 208-218"},"PeriodicalIF":2.6,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mod.2018.07.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36352472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}