scholarly journals Lin28a/let-7 Pathway Modulates the Hox Code via Polycomb Regulation during Axial Patterning in Vertebrates

2019 ◽  
Author(s):  
Tempei Sato ◽  
Kensuke Kataoka ◽  
Yoshiaki Ito ◽  
Shigetoshi Yokoyama ◽  
Masafumi Inui ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Body Plan ◽  
The Body ◽  
Regulatory Pathway ◽  
Tight Control ◽  
Axial Patterning ◽  
Spatiotemporal Expression ◽  
Hox Code

AbstractThe body plan along the anteroposterior axis and regional identities are specified by the spatiotemporal expression of Hox genes. Multistep controls are required for their unique expression patterns; however, the molecular mechanisms behind the tight control of Hox genes are not fully understood. In this study, we demonstrated that the Lin28a/let-7 reciprocal regulatory pathway is critical for vertebral specification. Lin28a−/− mice exhibited homeotic transformations of vertebrae which were caused by the global dysregulation of posterior Hox genes. The accumulation of let-7-family microRNAs in Lin28a−/− mice resulted in the reduction of PRC1 occupancy at the Hox cluster loci by targeting Cbx2. Consistently, Lin28a loss in embryonic stem-like cells led to aberrant induction of posterior Hox genes, which was rescued by the knockdown of let-7-family microRNAs. These results suggest that Lin28/let-7 pathway is possibly involved in the modulation of the “Hox code” via Polycomb regulation during axial patterning in vertebrates.

scholarly journals Lin28a/let-7 pathway modulates the Hox code via Polycomb regulation during axial patterning in vertebrates

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tempei Sato ◽  
Kensuke Kataoka ◽  
Yoshiaki Ito ◽  
Shigetoshi Yokoyama ◽  
Masafumi Inui ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Hox Genes ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
The Body ◽  
Tight Control ◽  
Tail Bud ◽  
Axial Patterning ◽  
Spatiotemporal Expression ◽  
Hox Code

The body plan along the anteroposterior axis and regional identities are specified by the spatiotemporal expression of Hox genes. Multistep controls are required for their unique expression patterns; however, the molecular mechanisms behind the tight control of Hox genes are not fully understood. In this study, we demonstrated that the Lin28a/let-7 pathway is critical for axial elongation. Lin28a–/– mice exhibited axial shortening with mild skeletal transformations of vertebrae, which were consistent with results in mice with tail bud-specific mutants of Lin28a. The accumulation of let-7 in Lin28a–/– mice resulted in the reduction of PRC1 occupancy at the Hox cluster loci by targeting Cbx2. Consistently, Lin28a loss in embryonic stem-like cells led to aberrant induction of posterior Hox genes, which was rescued by the knockdown of let-7. These results suggest that the Lin28/let-7 pathway is involved in the modulation of the ‘Hox code’ via Polycomb regulation during axial patterning.

scholarly journals Expression patterns of signalling molecules and transcription factors in the early rabbit embryo and their significance for modelling amniote axis formation

2021 ◽  
Author(s):  
Ruben Plöger ◽  
Christoph Viebahn
Keyword(s):  
Transcription Factors ◽  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Body Plan ◽  
The Body ◽  
Anchor Point ◽  
Axis Formation ◽  
Point Model ◽  
Signalling Molecules ◽  
Rabbit Embryo

AbstractThe anterior-posterior axis is a central element of the body plan and, during amniote gastrulation, forms through several transient domains with specific morphogenetic activities. In the chick, experimentally proven activity of signalling molecules and transcription factors lead to the concept of a ‘global positioning system’ for initial axis formation whereas in the (mammotypical) rabbit embryo, a series of morphological or molecular domains are part of a putative ‘three-anchor-point model’. Because circular expression patterns of genes involved in axis formation exist in both amniote groups prior to, and during, gastrulation and may thus be suited to reconcile these models, the expression patterns of selected genes known in the chick, namely the ones coding for the transcription factors eomes and tbx6, the signalling molecule wnt3 and the wnt inhibitor pkdcc, were analysed in the rabbit embryonic disc using in situ hybridisation and placing emphasis on their germ layer location. Peripheral wnt3 and eomes expression in all layers is found initially to be complementary to central pkdcc expression in the hypoblast during early axis formation. Pkdcc then appears — together with a posterior-anterior gradient in wnt3 and eomes domains — in the epiblast posteriorly before the emerging primitive streak is marked by pkdcc and tbx6 at its anterior and posterior extremities, respectively. Conserved circular expression patterns deduced from some of this data may point to shared mechanisms in amniote axis formation while the reshaping of localised gene expression patterns is discussed as part of the ‘three-anchor-point model’ for establishing the mammalian body plan.

scholarly journals Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids

2020 ◽  
Author(s):  
Ali Hashmi ◽  
Sham Tlili ◽  
Pierre Perrin ◽  
Alfonso Martinez-Arias ◽  
Pierre-François Lenne
Keyword(s):  
Spatial Organization ◽  
Embryonic Stem ◽  
Cell Movement ◽  
Body Plan ◽  
The Body ◽  
State Transitions ◽  
Sequence Of Events ◽  
Complex Process ◽  
Cell Layers ◽  
Sorting Process

AbstractShaping the animal body plan is a complex process that involves the spatial organization and patterning of different cell layers. Recent advances in live imaging have started to unravel the cellular choreography underlying this process in mammals, however, the sequence of events transforming an unpatterned cell ensemble into structured territories is largely unknown. Here, using 3D aggregates of mouse embryonic stem cells, we study the formation of one of the three germ layers, the endoderm. We show that the endoderm is generated from an epiblast-like state by a three-step mechanism: a release of islands of Ecadherin expressing cells, their flow toward the aggregate tip, and their segregation. Unlike the prevailing view, this mechanism does not require epithelial-to-mesenchymal transitions and vice-versa but rather a fragmentation, which is mediated by Wnt/β-catenin, and a sorting process. Our data emphasize the role of signaling and cell flows in the establishment of the body plan.

scholarly journals Hex Hox: De Novo Transcriptome Assembly and Embryonic Hox Gene Expression in the Burrowing Mayfly Hexagenia Limbata (Ephemeridae)

2021 ◽  
Author(s):  
Christopher J Gonzalez ◽  
Tobias R Hildebrandt ◽  
Brigid C O'Donnell
Keyword(s):  
Hox Genes ◽  
Transcriptome Assembly ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Body Plan ◽  
The Body ◽  
Phylogenetic Position ◽  
Developmental Genetics ◽  
Early Instar ◽  
Hexagenia Limbata

Abstract Background: Hox genes are key regulators of appendage development in the insect body plan. The body plan of Mayfly (Ephemeroptera) nymphs differs due to the presence of evolutionarily significant abdominal appendages called gills. Despite mayflies’ basal phylogenetic position and novel morphology amongst insects, little is known of their developmental genetics. Here we present an annotated transcriptome for the mayfly Hexagenia limbata, with annotated sequences for putative Hox peptides and embryonic expression profiles for the Hox genes Antp and Ubx/abd-A. Results: Transcriptomic sequencing of early instar H. limbata nymphs yielded a high-quality assembly of 83,795 contigs, of which 22,975 were annotated against Folsomia candida, Nilaparvata lugens, Zootermopsis nevadensis and UniRef90 protein databases. Peptide annotations included eight of the ten canonical Hox genes (lab, pb, Dfd, Scr, Antp, Ubx, abd-A and Abd-B), most of which contained all functional domains and motifs conserved in insects. Expression patterns of Antp and Ubx/abd-A in H. limbata were visualized from early to late embryogenesis, and are also highly conserved with patterns reported for other non-holometabolous insects.Conclusions: We present evidence that both H. limbata Hox peptide sequences and embryonic expression patterns for Antp and Ubx/abd-A are extensively conserved with other insects. These findings suggest mayfly Antp and Ubx/abd-A play similar appendage promoting and repressing roles in the thorax and abdomen, respectively. The identified expression of Ubx and abd-A in early instar nymphs further suggests that mayfly gill development is not subject to Ubx or abd-A repression. Previous studies have shown that insect Ubx and abd-A repress appendages by inhibiting their distal structures, which can permit the development of proximal appendage types. In line with past morphology-based work, we propose that mayfly gills are proximal appendage structures, possibly homologous to the proximal appendage structures of crustaceans.

HyAlx, an aristaless-related gene, is involved in tentacle formation in hydra

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4743-4752 ◽  
Author(s):  
K.M. Smith ◽  
L. Gee ◽  
H.R. Bode
Keyword(s):  
Expression Patterns ◽  
Reaction Diffusion ◽  
The Body ◽  
Related Gene ◽  
Axial Patterning ◽  
Bud Formation ◽  
Isolation And Characterization ◽  
Reaction Diffusion Model ◽  
Head Regeneration

Developmental gradients are known to play important roles in axial patterning in hydra. Current efforts are directed toward elucidating the molecular basis of these gradients. We report the isolation and characterization of HyAlx, an aristaless-related gene in hydra. The expression patterns of the gene in adult hydra, as well as during bud formation, head regeneration and the formation of ectopic head structures along the body column, indicate the gene plays a role in the specification of tissue for tentacle formation. The use of RNAi provides more direct evidence for this conclusion. The different patterns of HyAlx expression during head regeneration and bud formation also provide support for a recent version of a reaction-diffusion model for axial patterning in hydra.

scholarly journals Enigma of Retrotransposon Biology in Mammalian Early Embryos and Embryonic Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Ying Yin ◽  
Liquan Zhou ◽  
Shuiqiao Yuan
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Alternative Promoters ◽  
Human Escs ◽  
Early Embryos ◽  
Regulatory Functions

Retrotransposons comprise a significant fraction of mammalian genome with unclear functions. Increasing evidence shows that they are not just remnants of ancient retroviruses but play important roles in multiple biological processes. Retrotransposons are epigenetically silenced in most somatic tissues and become reactivated in early embryos. Notably, abundant retrotransposon expression in mouse embryonic stem cells (ESCs) marks transient totipotency status, while retrotransposon enrichment in human ESCs indicates naive-like status. Some retrotransposon elements retained the capacity to retrotranspose, such as LINE1, producing genetic diversity or disease. Some other retrotransposons reside in the vicinity of endogenous genes and are capable of regulating nearby genes and cell fate, possibly through providing alternative promoters, regulatory modules, or orchestrating high-order chromatin assembly. In addition, retrotransposons may mediate epigenetic memory, regulate gene expression posttranscriptionally, defend virus infection, and so on. In this review, we summarize expression patterns and regulatory functions of different retrotransposons in early embryos and ESCs, as well as document molecular mechanisms controlling retrotransposon expression and their potential functions. Further investigations on the regulatory network of retrotransposons in early embryogenesis and ESCs will provide valuable insights and a deeper understanding of retrotransposon biology. Additionally, endeavors made to unveil the roles of these mysterious elements may facilitate stem cell status conversion and manipulation of pluripotency.

scholarly journals Orchestrating morphogenesis: building the body plan by cell shape changes and movements

Development ◽  
2020 ◽  
Vol 147 (17) ◽  
pp. dev191049 ◽  
Author(s):  
Kia Z. Perez-Vale ◽  
Mark Peifer
Keyword(s):  
Cell Shape ◽  
Molecular Mechanisms ◽  
Fruit Fly ◽  
Body Plan ◽  
The Body ◽  
Collective Cell Migration ◽  
Convergent Extension ◽  
Apical Constriction ◽  
Cell Shape Changes ◽  
Shape Changes

ABSTRACTDuring embryonic development, a simple ball of cells re-shapes itself into the elaborate body plan of an animal. This requires dramatic cell shape changes and cell movements, powered by the contractile force generated by actin and myosin linked to the plasma membrane at cell-cell and cell-matrix junctions. Here, we review three morphogenetic events common to most animals: apical constriction, convergent extension and collective cell migration. Using the fruit fly Drosophila as an example, we discuss recent work that has revealed exciting new insights into the molecular mechanisms that allow cells to change shape and move without tearing tissues apart. We also point out parallel events at work in other animals, which suggest that the mechanisms underlying these morphogenetic processes are conserved.

scholarly journals Evidence for Bone Marrow Adult Stem Cell Plasticity: Properties, Molecular Mechanisms, Negative Aspects, and Clinical Applications of Hematopoietic and Mesenchymal Stem Cells Transdifferentiation

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ivana Catacchio ◽  
Simona Berardi ◽  
Antonia Reale ◽  
Annunziata De Luisi ◽  
Vito Racanelli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adult Stem Cells ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Clinical Importance ◽  
The Body ◽  
Differentiation Potential ◽  
New Findings

In contrast to the pluripotentembryonic stem cells(ESCs) which are able to give rise to all cell types of the body, mammalianadult stem cells(ASCs) appeared to be more limited in their differentiation potential and to be committed to their tissue of origin. Recently, surprising new findings have contradicted central dogmas of commitment of ASCs by showing their plasticity to differentiate across tissue lineage boundaries, irrespective of classical germ layer designations. The present paper supports the plasticity of thebone marrow stem cells(BMSCs), bringing the most striking and the latest evidences of the transdifferentiation properties of thebone marrow hematopoietic and mesenchymal stem cells(BMHSCs, and BMMSCs), the two BM populations of ASCs better characterized. In addition, we report the possible mechanisms that may explain these events, outlining the clinical importance of these phenomena and the relative problems.

scholarly journals Transcriptomic analysis of sea star development through metamorphosis to the highly derived pentameral body plan with a focus on neural transcription factors

DNA Research ◽  
2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Maria Byrne ◽  
Demian Koop ◽  
Dario Strbenac ◽  
Paula Cisternas ◽  
Regina Balogh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Expression Patterns ◽  
Body Plan ◽  
Sea Star ◽  
Neural Genes ◽  
Transcription Factor Genes ◽  
Juvenile Stages ◽  
Sensory Structures

Abstract The Echinodermata is characterized by a secondarily evolved pentameral body plan. While the evolutionary origin of this body plan has been the subject of debate, the molecular mechanisms underlying its development are poorly understood. We assembled a de novo developmental transcriptome from the embryo through metamorphosis in the sea star Parvulastra exigua. We use the asteroid model as it represents the basal-type echinoderm body architecture. Global variation in gene expression distinguished the gastrula profile and showed that metamorphic and juvenile stages were more similar to each other than to the pre-metamorphic stages, pointing to the marked changes that occur during metamorphosis. Differential expression and gene ontology (GO) analyses revealed dynamic changes in gene expression throughout development and the transition to pentamery. Many GO terms enriched during late metamorphosis were related to neurogenesis and signalling. Neural transcription factor genes exhibited clusters with distinct expression patterns. A suite of these genes was up-regulated during metamorphosis (e.g. Pax6, Eya, Hey, NeuroD, FoxD, Mbx, and Otp). In situ hybridization showed expression of neural genes in the CNS and sensory structures. Our results provide a foundation to understand the metamorphic transition in echinoderms and the genes involved in development and evolution of pentamery.

scholarly journals Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Ryuichiro Nakato ◽  
Youichiro Wada ◽  
Ryo Nakaki ◽  
Genta Nagae ◽  
Yuki Katou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Transcriptional Regulation ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
Expression Patterns ◽  
Comprehensive Analysis ◽  
The Body ◽  
Chromatin Interaction ◽  
Marker Genes

Abstract Background Endothelial cells (ECs) make up the innermost layer throughout the entire vasculature. Their phenotypes and physiological functions are initially regulated by developmental signals and extracellular stimuli. The underlying molecular mechanisms responsible for the diverse phenotypes of ECs from different organs are not well understood. Results To characterize the transcriptomic and epigenomic landscape in the vascular system, we cataloged gene expression and active histone marks in nine types of human ECs (generating 148 genome-wide datasets) and carried out a comprehensive analysis with chromatin interaction data. We developed a robust procedure for comparative epigenome analysis that circumvents variations at the level of the individual and technical noise derived from sample preparation under various conditions. Through this approach, we identified 3765 EC-specific enhancers, some of which were associated with disease-associated genetic variations. We also identified various candidate marker genes for each EC type. We found that the nine EC types can be divided into two subgroups, corresponding to those with upper-body origins and lower-body origins, based on their epigenomic landscape. Epigenomic variations were highly correlated with gene expression patterns, but also provided unique information. Most of the deferentially expressed genes and enhancers were cooperatively enriched in more than one EC type, suggesting that the distinct combinations of multiple genes play key roles in the diverse phenotypes across EC types. Notably, many homeobox genes were differentially expressed across EC types, and their expression was correlated with the relative position of each organ in the body. This reflects the developmental origins of ECs and their roles in angiogenesis, vasculogenesis and wound healing. Conclusions This comprehensive analysis of epigenome characterization of EC types reveals diverse transcriptional regulation across human vascular systems. These datasets provide a valuable resource for understanding the vascular system and associated diseases.

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