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

Author(s):  
Ruben Plöger ◽  
Christoph Viebahn

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.

2018 ◽  
Vol 285 (1881) ◽  
pp. 20180296 ◽  
Author(s):  
Pei-Yun Cong ◽  
Thomas H. P. Harvey ◽  
Mark Williams ◽  
David J. Siveter ◽  
Derek J. Siveter ◽  
...  

Chancelloriids are an extinct group of spiny Cambrian animals of uncertain phylogenetic position. Despite their sponge-like body plan, their spines are unlike modern sponge spicules, but share several features with the sclerites of certain Cambrian bilaterians, notably halkieriids. However, a proposed homology of these ‘coelosclerites' implies complex transitions in body plan evolution. A new species of chancelloriid, Allonnia nuda , from the lower Cambrian (Stage 3) Chengjiang Lagerstätte is distinguished by its large size and sparse spination, with modified apical sclerites surrounding an opening into the body cavity. The sclerite arrangement in A. nuda and certain other chancelloriids indicates that growth involved sclerite addition in a subapical region, thus maintaining distinct zones of body sclerites and apical sclerites. This pattern is not seen in halkieriids, but occurs in some modern calcarean sponges. With scleritome assembly consistent with a sponge affinity, and in the absence of cnidarian- or bilaterian-grade features, it is possible to interpret chancelloriids as sponges with an unusually robust outer epithelium, strict developmental control of body axis formation, distinctive spicule-like structures and, by implication, minute ostia too small to be resolved in fossils. In this light, chancelloriids may contribute to the emerging picture of high disparity among early sponges.


2021 ◽  
Author(s):  
Christopher J Gonzalez ◽  
Tobias R Hildebrandt ◽  
Brigid C O'Donnell

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.


1995 ◽  
Vol 349 (1329) ◽  
pp. 313-319 ◽  

Homeobox genes encode transcription factors that carry out diverse roles during development. They are widely distributed among eukaryotes, but appear to have undergone an extensive radiation in the earliest metazoa, to generate a range of homeobox subclasses now shared between diverse metazoan phyla. The Hox genes comprise one of these subfamilies, defined as much by conserved chromosomal organization and expression as by sequence characteristics. These Hox genes act as markers of position along the antero—posterior axis of the body in nematodes, arthropods, chordates, and by implication, most other triploblastic phyla. In the arthropods this role is visualized most clearly in the control of segment identity. Exactly how Hox genes control the structure of segments is not yet understood, but their differential deployment between segments provides a model for the basis of segment diversity. Within the arthropods, distantly related taxonomic groups with very different body plans (insects, crustaceans) may share the same set of Hox genes. The expression of these Hox genes provides a new character to define the homology of different body regions. Comparisons of Hox gene deployment between insects and a branchiopod crustacean suggest a novel model for the derivation of the insect body plan.


Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 341
Author(s):  
Kimiko Takebayashi-Suzuki ◽  
Atsushi Suzuki

During embryonic development in vertebrates, morphogens play an important role in cell fate determination and morphogenesis. Bone morphogenetic proteins (BMPs) belonging to the transforming growth factor-β (TGF-β) family control the dorsal–ventral (DV) patterning of embryos, whereas other morphogens such as fibroblast growth factor (FGF), Wnt family members, and retinoic acid (RA) regulate the formation of the anterior–posterior (AP) axis. Activation of morphogen signaling results in changes in the expression of target genes including transcription factors that direct cell fate along the body axes. To ensure the correct establishment of the body plan, the processes of DV and AP axis formation must be linked and coordinately regulated by a fine-tuning of morphogen signaling. In this review, we focus on the interplay of various intracellular regulatory mechanisms and discuss how communication among morphogen signaling pathways modulates body axis formation in vertebrate embryos.


2019 ◽  
Vol 63 (11-12) ◽  
pp. 631-639
Author(s):  
Michael Elsy ◽  
Abigail Rowbotham ◽  
Hannah Lord ◽  
Harry V. Isaacs ◽  
Mary E. Pownall

Fibroblast growth factors (FGFs) comprise a family of signalling molecules with essential roles in early embryonic development across animal species. The role of FGFs in mesoderm formation and patterning in Xenopus has been particularly well studied. However, little is known about FGF16 in Xenopus. Using in situ hybridisation, we uncover the expression pattern of FGF16 during early Xenopus laevis development, which has not been previously described. We show that the zygotic expression of FGF16 is activated in the mesoderm of the early gastrula as a ring around the blastopore, with its first accumulation at the dorsal side of the embryo. Later, FGF16 expression is found in the otic vesicle, the branchial arches and the anterior pituitary, as well as in the chordal neural hinge region of the tailbud. In addition, we show that FGF16 can activate the MAPK pathway and expression of sp5 and sp5l. Like FGF16, sp5 is expressed in the otic vesicle and the branchial arches, with all three of these genes being expressed in the tailbud. These data provide evidence that FGF16 is present in the early mesoderm and can activate the expression of developmentally important transcription factors.


2019 ◽  
Author(s):  
Tempei Sato ◽  
Kensuke Kataoka ◽  
Yoshiaki Ito ◽  
Shigetoshi Yokoyama ◽  
Masafumi Inui ◽  
...  

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.


2018 ◽  
Author(s):  
Julien Rougeot ◽  
Naomi D. Chrispijn ◽  
Marco Aben ◽  
Dei M. Elurbe ◽  
Karolina M. Andralojc ◽  
...  

AbstractPolycomb group (PcG) proteins are transcriptional repressors that are important regulators of cell fate during embryonic development. Among them, Ezh2 is responsible for catalyzing the epigenetic repressive mark H3K27me3 and is essential for animal development. The ability of zebrafish embryos lacking both maternal and zygotic ezh2 to form a normal body plan provides a unique model to comprehensively study Ezh2 function during early development in vertebrates. By using a multi-omics approach, we found that Ezh2 is required for the deposition of H3K27me3 and is essential for the recruitment of Polycomb group protein Rnf2. However, and despite the complete absence of PcG-associated epigenetic mark and proteins, only minor changes in H3K4me3 deposition and gene and protein expression occurred. These changes were mainly due to local deregulation of transcription factors outside their normal expression boundaries. Altogether, our results in zebrafish show that Polycomb-mediated gene repression is important right after the body plan is formed to maintain spatially restricted expression profiles of transcription factors and highlight the differences that exist in the timing of PcG protein action between vertebrate species.Summary statementOur unique zebrafish model of maternal and zygotic mutant for the Polycomb group gene ezh2 reveals major conserved and divergent mechanisms in epigenetic gene repression during vertebrate development.


2017 ◽  
Author(s):  
Mickael Orgeur ◽  
Marvin Martens ◽  
Georgeta Leonte ◽  
Sonya Nassari ◽  
Marie-Ange Bonnin ◽  
...  

AbstractBackgroundConnective tissues support, connect and separate tissues and organs, playing crucial roles in development, homeostasis and fibrosis. Cell specification and differentiation is triggered by the activity of specific transcription factors. While key transcription factors have been identified for differentiation processes of most tissues, connective tissue differentiation remains largely unstudied.ResultsTo gain insight into the regulatory cascades involved in connective tissue differentiation, we selected five zinc finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in the differentiation of mesenchymal cells into connective tissue subtypes. We combined RNA-seq with ChIP-seq profiling in chick limb cells following overexpression of individual transcription factors. We identified a set of common genes regulated by all five transcription factors, which constitutes a connective tissue core expression set. This common core was enriched in genes associated with axon guidance and myofibroblast signature. In addition, each of the transcription factors regulated a different set of extracellular matrix components and signalling molecules, which define local molecular niches important for connective tissue development and function.ConclusionsThe established regulatory network identifies common and distinct molecular signatures downstream of five connective tissue-associated transcription factors and provides insight into the signalling pathways governing limb connective tissue differentiation. It also suggests a concept whereby local molecular niches can be created via the expression of specific transcription factors impinging on the specification of microenvironments.


Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 26-28
Author(s):  
Jonathan Dawson ◽  
Richard Oreffo

Gels made from clay could provide an environment able to stimulate stem-cells due to their ability to bind biological molecules. That molecules stick to clay has been known by scientists since the 1960s. Doctors observed that absorption into the blood stream of certain drugs was severely reduced when patients were also receiving clay-based antacid or anti-diarrhoeal treatments. This curious phenomenon was realized to be due to binding of the drugs by clay particles. This interaction is now routinely harnessed in the design of tablets to carefully control the release and action of a drug. Dr Dawson now proposes to use this property of clay to create micro-environments that could stimulate stem cells to regenerate damaged tissues such as bone, cartilage or skin. The rich electrostatic properties of nano (1 millionth of a millimetre) -scale clay particles which mediate these interactions could allow two hurdles facing the development of stem-cell based regenerative therapies to be overcome simultaneously. The first challenge - to deliver and hold stem cells at the right location in the body - is met by the ability of clays to self-organise into gels via the electrostatic interactions of the particles with each other. Cells mixed with a low concentration (less than 4%) of clay particles can be injected into the body and held in the right place by the gel, eliminating, in many situations, the need for surgery. Clay particles can also interact with large structural molecules (polymers) which are frequently used in the development of materials (or 'scaffolds'), designed to host stem cells. These interactions can greatly improve the strength of such structures and could be applied to preserve their stability at the site of injury until regeneration is complete. While several gels and scaffold materials have been designed to deliver and hold stem cells at the site of regeneration, the ability of clay nanoparticles to overcome a second critical hurdle facing stem-cell therapy is what makes them especially exciting. Essential to directing the activity of stem-cells is the carefully controlled provision of key biological signalling molecules. However, the open structures of conventional scaffolds or gels, while essential for the diffusion of nutrients to the cells, means their ability to hold the signalling molecules in the same location as the cells is limited. The ability of clay nano-particles to bind biological molecules presents a unique opportunity to create local environments at a site of injury or disease that can stimulate and control stem-cell driven repair. Dr Dawson's early studies investigated the ability of clay gels to stimulate the growth of new blood vessels by incorporating a key molecular signal that stimulates this process, vascular endothelial growth factor (VEGF). In a manner reminiscent of the observations made in the 60s, Dr Dawson and colleagues observed that adding a drop of clay gel to a solution containing VEGF caused, after a few hours, the disappearance of VEGF from the solution as it became bound to the gel. When placed in an experimental injury model, the gel-bound VEGF stimulated a cluster of new blood vessels to form. These exciting results indicate the potential of clay nanoparticles to create tailor-made micro-environments to foster stem cell regeneration. Dr Dawson is developing this approach as a means of first exploring the biological signals necessary to successfully control stem cell behaviour for regeneration and then, using the same approach, to provide stem cells with these signals to stimulate regeneration in the body. The project will seek to test this approach to regenerate bone lost to cancer or hip replacement failure. If successful the same technology may be applied to harness stem cells for the treatment of a whole host of different scenarios, from burn victims to those suffering with diabetes or Parkinson's.


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