Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “mesoderm”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources

The role of the dorsal lip in the induction of heart mesoderm in Xenopus laevis.

We have examined the tissue interactions responsible for the expression of heart-forming potency during gastrulation. By comparing the specification of different regions of the marginal zone, we show that heart-forming potency is expressed only in explants containing both the dorsal lip of the blastopore and deep mesoderm between 30 degrees and 45 degrees lateral to the dorsal midline. Embryos from which both of these 30 degrees-45 degrees dorsolateral regions have been removed undergo heart formation in two thirds of cases, as long as the dorsal lip is left intact. If the dorsal lip is removed along with the 30 degrees-45 degrees regions, heart formation does not occur. These results indicate that the dorsolateral deep mesoderm must interact with the dorsal lip in order to express heart-forming potency. Transplantation of the dorsal lip into the ventral marginal zone of host embryos results in the formation of a secondary axis; in over half of cases, this secondary axis includes a heart derived from the host mesoderm. These findings suggest that the establishment of heart mesoderm is initiated by a dorsalizing signal from the dorsal lip of the blastopore.

Animals↗

Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos.

During Drosophila embryogenesis homeotic genes control the developmental diversification of body structures. The genes probably coordinate the expression of as yet unidentified target genes that carry out cell differentiation processes. At least four homeotic genes expressed in the visceral mesoderm are required for midgut morphogenesis. In addition, two growth factor homologs are expressed in specific regions of the visceral mesoderm surrounding the midgut epithelium. One of these, decapentaplegic (dpp), is a member of the transforming growth factor beta (TGF-beta) family; the other, wingless (wg), is a relative of the mammalian proto-oncogene int-1. Here we show that the spatially restricted expression of dpp in the visceral mesoderm is regulated by the homeotic genes Ubx and abd-A. Ubx is required for the expression of dpp while abd-A represses dpp. One consequence of dpp expression is the induction of labial (lab) in the underlying endoderm cells. In addition, abd-A function is required for the expression of wg in the visceral mesoderm posterior to the dpp-expressing cells. The two growth factor genes therefore are excellent candidates for target genes that are directly regulated by the homeotic genes.

Animals↗

Nuclear translocation of fibroblast growth factor during Xenopus mesoderm induction.

Mesoderm induction, the earliest inductive cell-cell interaction in vertebrate embryogenesis, is thought to be mediated by polypeptide growth factors including fibroblast growth factor (FGF). Here we present an immunocytochemical analysis of FGF during mesoderm induction in Xenopus laevis. Antibodies to both basic and acidic FGF were immunoreactive with oocytes and early embryos. Immunostaining was predominantly intracellular and was concentrated in the marginal zone and vegetal pole throughout cleavage and blastula stages. In addition, basic FGF (bFGF) antibodies showed intense nuclear staining in these regions, at and following the mid-blastula transition, when embryonic transcription begins. Acidic FGF (aFGF) also appeared in some nuclei at these stages. Taken together the evidence suggests that FGF is prepositioned in mesoderm-forming regions and is actively involved in mesoderm induction in vivo.

Animals↗

DVR-4 (bone morphogenetic protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction.

Establishment of mesodermal tissues in the amphibian body involves a series of inductive interactions probably elicited by a variety of peptide growth factors. Results reported here suggest that mesodermal patterning involves an array of signalling molecules including DVR-4, a TGF-beta-like molecule. We show that ectopic expression of DVR-4 causes embryos to develop with an overall posterior and/or ventral character, and that DVR-4 induces ventral types of mesoderm in animal cap explants. Moreover, DVR-4 overrides the dorsalizing effects of activin. DVR-4 is therefore the first molecule reported both to induce posteroventral mesoderm and to counteract dorsalizing signals such as activin. Possible interactions between these molecules resulting in establishment of the embryonic body plan are discussed.

Activins↗

MHox: a mesodermally restricted homeodomain protein that binds an essential site in the muscle creatine kinase enhancer.

Myogenic helix-loop-helix (HLH) proteins, such as myogenin and MyoD, can activate muscle-specific transcription when introduced into a variety of nonmuscle cell types. Whereas cells of mesodermal origin are especially permissive to the actions of these myogenic regulators, many other cell types are refractory to myogenic conversion by them. Here we describe a novel homeodomain protein, MHox, that binds an A+T-rich element in the muscle creatine kinase (MCK) enhancer that is essential for muscle-specific transcription and trans-activation by myogenic HLH proteins. MHox is completely restricted to mesodermally derived cell types during embryogenesis and to established cell lines of mesodermal origin. In contrast to most other homeobox genes, MHox expression is excluded from the nervous system, with the highest levels observed in limb bud and visceral arches. In adult mice, MHox is expressed at high levels in skeletal muscle, heart and uterus. The DNA-binding properties and pattern of MHox expression are unique among homeobox genes and suggest a role for MHox as a transcriptional regulator that participates in the establishment of diverse mesodermal cell types.

Amino Acid Sequence↗

Ultrabithorax is a regulator of beta 3 tubulin expression in the Drosophila visceral mesoderm.

beta 3 tubulin expression accompanies the specification and differentiation of the Drosophila mesoderm. The genetic programs involved in these processes are largely unknown. Our previous studies on the regulation of the beta 3 tubulin gene have shown that upstream sequences guide the expression in the somatic musculature, while regulatory elements in the first intron are necessary for expression in the visceral musculature. To further analyse this mode of regulation, which reflects an early embryonic specification program, we undertook a more detailed analysis of the regulatory capabilities of the intron. The results reveal not only a certain degree of redundancy in the cis-acting elements, which act at different developmental stages in the same mesodermal derivatives, but they also demonstrate in the visceral mesoderm, which forms a continuous epithelium along the body axis of the embryo, an early action of regulators guiding gene expression along the anterior-posterior axis of the embryo: an enhancer element in the intron leads to expression in a subdomain restricted along the anterior-posterior axis. This pattern is altered in mutants in the homeotic gene Ultrabithorax (Ubx), whereas ectopic Ubx expression leads to activity of the enhancer in the entire visceral mesoderm. So this element is likely to be a target of homeotic genes, which would define the beta 3 tubulin gene as a realisator gene under the control of selector genes.

Animals↗

Mesoderm formation in Xenopus ectodermal explants overexpressing Xwnt8: evidence for a cooperating signal reaching the animal pole by gastrulation.

It is demonstrated here that the ability of injected Xwnt8 RNA to trigger mesoderm formation in Xenopus presumptive ectoderm (animal caps) depends on the time of explantation. Animal caps isolated from Xwnt8 injected embryos at the late blastula/early gastrula stages differentiate mesodermal tissues whereas caps isolated from early blastula do not. This finding suggests that an endogenous signal reaches the animal cap by the late blastula stage and cooperates with Xwnt8 to induce mesoderm. Similarly, late animal caps isolated at st. 10 from lithium-treated embryos, but not those from control embryos, elongate and express muscle-specific actin transcripts. In addition, the data presented suggests that the cooperating signal is distributed homogeneously with respect to the future dorsoventral axis and may require FGF- and activin-dependent signal transduction pathways. These observations support a model in which mesoderm is induced in vivo by a combined action of several different signals.

Animals↗

Mesoderm induction by activin requires FGF-mediated intracellular signals.

We have examined the role of FGF signaling during activin-mediated mesoderm induction in Xenopus. Using dominant inhibitory mutants of FGF signal transducers to disrupt the FGF-signaling pathway at the plasma membrane or in the cytosol prevents animal cap blastomeres from expressing several mesodermal markers in response to exogenous activin. Dominant inhibitory mutants of the FGF receptor, c-ras or c-raf inhibit the ability of activin to induce molecular markers of both dorsal and ventral mesoderm including Xbra, Mix1 and Xnot. Some transcriptional responses to activin such as goosecoid and Xwnt8 are inhibited less effectively than others, however, suggesting that there may differing requirements for an FGF signal in the responses of mesoderm-specific genes to activin induction. Despite the requirement for this signaling pathway during activin induction, downstream components of this pathway are not activated in response to activin, suggesting that activin does not signal directly through this pathway.

Activins↗

Muscle pattern diversification in Drosophila is determined by the autonomous function of homeotic genes in the embryonic mesoderm.

Muscle diversification in the Drosophila embryo is manifest in a stereotyped array of myofibers that exhibit distinct segment-specific patterns. Here it is shown that the homeotic genes of the Bithorax complex control the identities of abdominal somatic muscles and their precursors by functioning directly in cells of the mesoderm. Whereas Ultrabithorax (Ubx) and abdominal-A (abd-A) have equivalent functions in promoting the formation of particular muscle precursors in the anterior abdominal segments, Abdominal-B (Abd-B) suppresses the development of these same myogenic cells in the posterior region of the abdomen. When expressed in the same mesodermal cells, however, either UBX or ABD-A can override the inhibitory influence of ABD-B, suggesting that these factors may compete in the regulation of common downstream genes. Furthermore, targeted ectopic expression of Ubx or abd-A indicates that these homeotic genes influence muscle cell fates by autonomous action in mesodermal cells. Muscle identity also appears to be sensitive to the level of UBX in myogenic precursors. Finally, these experiments reveal that homeotic cues specific to both the mesoderm and the ectoderm cooperate to specify the pattern of muscle attachment sites.

Animals↗

Xenopus VegT RNA is localized to the vegetal cortex during oogenesis and encodes a novel T-box transcription factor involved in mesodermal patterning.

An RNA localized to the vegetal cortex of Xenopus oocytes encodes a novel T-box protein (VegT) capable of inducing either dorsal or posterior ventral mesoderm at different times in development. VegT is a nuclear protein and its C-terminal domain can activate transcription in a yeast reporter assay, observations consistent with VegT functioning as a transcription factor. Zygotic expression is dynamic along the dorsoventral axis, with transcripts first expressed in the dorsal marginal zone. By the end of gastrulation, VegT is expressed exclusively in posterior ventral and lateral mesoderm and is excluded from the notochord. Later expression is confined to a subset of Rohon-Beard cells, a type of primary sensory neuron. In animal cap assays, VegT is capable of converting prospective ectoderm into ventral lateral mesoderm. Such ectopic expression of VegT induces its own expression as well as that of Xwnt-8 in caps, suggesting that a Wnt pathway may be involved. Mis-expression of VegT in dorsal animal blastomeres fated to contribute to brain suppresses head formation. Our results suggest that VegT is a localized transcription factor, which operates sequentially in several developmental pathways during embryogenesis, including dorsoventral and posterior patterning of mesoderm.

Amino Acid Sequence↗

A differential display strategy identifies Cryptic, a novel EGF-related gene expressed in the axial and lateral mesoderm during mouse gastrulation.

We have developed a differential display screening approach to identify mesoderm-specific genes, relying upon the differentiation of embryonic stem (ES) cells in vitro. Using this strategy, we have isolated a novel murine gene that encodes a secreted molecule containing a variant epidermal growth factor-like (EGF) motif. We named this gene Cryptic, based on its predicted protein sequence similarity with Cripto, which encodes an EGF-related growth factor. Based on their strong sequence similarities, we propose that Cryptic, Cripto, and the Xenopus FRL-1 gene define a new family of growth factor-like molecules, which we name the 'CFC' (Cripto, Frl-1, and Cryptic) family. Analysis of Cryptic expression by in situ hybridization shows that it is expressed during gastrulation in two spatial domains that correspond to the axial and lateral mesoderm. In the first domain of expression, Cryptic expression is progressively localized to the anterior primitive streak, the head process, and the node and notochordal plate. In the second domain, Cryptic expression is initially concentrated in the lateral region of the egg cylinder, and is later found circumferentially in the intermediate and lateral plate mesoderm. Furthermore, Cryptic expression can also be detected at the early head-fold stage in the midline neuroectoderm, and consequently is an early marker for the prospective floor plate of the neural tube. Expression of Cryptic ceases at the end of gastrulation, and has not been observed in later embryonic stages or in adult tissues. Thus, Cryptic encodes a putative signaling molecule whose expression suggests potential roles in mesoderm and/or neural patterning during gastrulation.

Amino Acid Sequence↗

Taste buds develop autonomously from endoderm without induction by cephalic neural crest or paraxial mesoderm.

Although it had long been believed that embryonic taste buds in vertebrates were induced to differentiate by ingrowing nerve fibers, we and others have recently shown that embryonic taste buds can develop normally in the complete absence of innervation. This leads to the question of which tissues, if any, induce the formation of taste buds in oropharyngeal endoderm. We proposed that taste buds, like many specialized epithelial cells, might arise via an inductive interaction between the endodermal epithelial cells that line the oropharynx and the adjacent mesenchyme that is derived from both cephalic neural crest and paraxial mesoderm. Using complementary grafting and explant culture techniques, however, we have now found that well-differentiated taste buds will develop in tissue completely devoid of neural crest and paraxial mesoderm derivatives. When the presumptive oropharyngeal region was removed from salamander embryos prior to the onset of cephalic neural crest migration, taste buds developed in grafts and explants coincident with their appearance in intact control embryos. Similarly, explants from neurulae in which movement of paraxial mesoderm had not yet begun also developed taste buds after 9-12 days in vitro. We conclude that neither cranial neural crest nor paraxial mesoderm is responsible for the induction of embryonic taste buds. Surprisingly, the ability to develop taste buds late in embryonic development seems to be an intrinsic feature of the oropharyngeal endoderm that is determined by the completion of gastrulation.

Ambystoma↗

The Notch ligand, X-Delta-2, mediates segmentation of the paraxial mesoderm in Xenopus embryos.

Segmentation of the vertebrate embryo begins when the paraxial mesoderm is subdivided into somites, through a process that remains poorly understood. To study this process, we have characterized X-Delta-2, which encodes the second Xenopus homolog of Drosophila Delta. Strikingly, X-Delta-2 is expressed within the presomitic mesoderm in a set of stripes that corresponds to prospective somitic boundaries, suggesting that Notch signaling within this region establishes a segmental prepattern prior to somitogenesis. To test this idea, we introduced antimorphic forms of X-Delta-2 and Xenopus Suppressor of Hairless (X-Su(H)) into embryos, and assayed the effects of these antimorphs on somite formation. In embryos expressing these antimorphs, the paraxial mesoderm differentiated normally into somitic tissue, but failed to segment properly. Both antimorphs also disrupted the segmental expression of X-Delta-2 and Hairy2A, a basic helix-loop-helix (bHLH) gene, within the presomitic mesoderm. These observations suggest that X-Delta-2, via X-Notch-1, plays a role in segmentation, by mediating cell-cell interactions that underlie the formation of a segmental prepattern prior to somitogenesis.

Animals↗

Thylacine 1 is expressed segmentally within the paraxial mesoderm of the Xenopus embryo and interacts with the Notch pathway.

The presomitic mesoderm of vertebrates undergoes a process of segmentation in which cell-cell interactions mediated by the Notch family of receptors and their associated ligands are involved. The vertebrate homologues of Drosophila &Dgr ; are expressed in a dynamic, segmental pattern within the presomitic mesoderm, and alterations in the function of these genes leads to a perturbed pattern of somite segmentation. In this study we have characterised Thylacine 1 which encodes a basic helix-loop-helix class transcription activator. Expression of Thylacine is restricted to the presomitic mesoderm, localising to the anterior half of several somitomeres in register with domains of X-Delta-2 expression. Ectopic expression of Thylacine in embryos causes segmentation defects similar to those seen in embryos in which Notch signalling is altered, and these embryos also show severe disruption in the expression patterns of the marker genes X-Delta-2 and X-ESR5 within the presomitic mesoderm. Finally, the expression of Thylacine is altered in embryos when Notch signalling is perturbed. These observations suggest strongly that Thylacine 1 has a role in the segmentation pathway of the Xenopus embryo, by interacting with the Notch signalling pathway.

Amino Acid Sequence↗

Zebrafish paraxial protocadherin is a downstream target of spadetail involved in morphogenesis of gastrula mesoderm.

Zebrafish paraxial protocadherin (papc) encodes a transmembrane cell adhesion molecule (PAPC) expressed in trunk mesoderm undergoing morphogenesis. Microinjection studies with a dominant-negative secreted construct suggest that papc is required for proper dorsal convergence movements during gastrulation. Genetic studies show that papc is a close downstream target of spadetail, gene encoding a transcription factor required for mesodermal morphogenetic movements. Further, we show that the floating head homeobox gene is required in axial mesoderm to repress the expression of both spadetail and papc, promoting notochord and blocking differentiation of paraxial mesoderm. The PAPC structural cell-surface protein may provide a link between regulatory transcription factors and the actual cell biological behaviors that execute morphogenesis during gastrulation.

Amino Acid Sequence↗

Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5.

Activation of myogenesis in newly formed somites is dependent upon signals derived from neighboring tissues, namely axial structures (neural tube and notochord) and dorsal ectoderm. In explants of paraxial mesoderm from mouse embryos, axial structures preferentially activate myogenesis through a Myf5-dependent pathway and dorsal ectoderm preferentially through a MyoD-dependent pathway. Here we report that cells expressing Wnt1 will preferentially activate Myf5 while cells expressing Wnt7a will preferentially activate MyoD. Wnt1 is expressed in the dorsal neural tube and Wnt7a in dorsal ectoderm in the early embryo, therefore both can potentially act in vivo to activate Myf5 and MyoD, respectively. Wnt4, Wnt5a and Wnt6 exert an intermediate effect activating both Myf5 and MyoD equivalently in paraxial mesoderm. Sonic Hedgehog synergises with both Wnt1 and Wnt7a in explants from E8.5 paraxial mesoderm but not in explants from E9.5 embryos. Signaling through different myogenic pathways may explain the rescue of muscle formation in Myf5 null embryos, which do not form an early myotome but later develop both epaxial and hypaxial musculature. Explants of unsegmented paraxial mesoderm contain myogenic precursors capable of expressing MyoD in response to signaling from a neural tube isolated from E10.5 embryos, the developmental stage when MyoD is present throughout the embryo. Myogenic cells cannot activate MyoD in response to signaling from a less mature neural tube. Together these data suggest that different Wnt molecules can activate myogenesis through different pathways such that commitment of myogenic precursors is precisely regulated in space and time to achieve the correct pattern of skeletal muscle development.

Animals↗

Evidence for a frizzled-mediated wnt pathway required for zebrafish dorsal mesoderm formation.

We have used zebrafish as a model system for the study of vertebrate dorsoventral patterning. We isolated a maternally expressed and dorsal organizer localized member of the frizzled family of wnt receptors. Wild-type and dominant, loss-of-function molecules in misexpression studies demonstrate frizzled function is necessary and sufficient for dorsal mesoderm specification. frizzled activity is antagonized by the action of GSK-3, and we show GSK-3 is also required for zebrafish dorsal mesoderm formation. frizzled cooperatively interacts with the maternally encoded zebrafish wnt8 protein in dorsal mesodermal fate determination. This frizzled -mediated wnt pathway for dorsal mesoderm specification provides the first evidence for the requirement of a wnt-like signal in vertebrate axis determination.

Amino Acid Sequence↗

The control of rostrocaudal pattern in the developing spinal cord: specification of motor neuron subtype identity is initiated by signals from paraxial mesoderm.

The generation of distinct classes of motor neurons is an early step in the control of vertebrate motor behavior. To study the interactions that control the generation of motor neuron subclasses in the developing avian spinal cord we performed in vivo grafting studies in which either the neural tube or flanking mesoderm were displaced between thoracic and brachial levels. The positional identity of neural tube cells and motor neuron subtype identity was assessed by Hox and LIM homeodomain protein expression. Our results show that the rostrocaudal identity of neural cells is plastic at the time of neural tube closure and is sensitive to positionally restricted signals from the paraxial mesoderm. Such paraxial mesodermal signals appear to control the rostrocaudal identity of neural tube cells and the columnar subtype identity of motor neurons. These results suggest that the generation of motor neuron subtypes in the developing spinal cord involves the integration of distinct rostrocaudal and dorsoventral patterning signals that derive, respectively, from paraxial and axial mesodermal cell groups.

Animals↗