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At least 613 records · Page 34Linked to original sources
PubMed1993

Mesodermal cell adhesion to fibronectin-rich fibrillar extracellular matrix is required for normal Rana pipiens gastrulation.

New observations on thin strips of cells from the leading edge of the involuting presumptive mesoderm explanted onto FN-coated substrate show a striking preferential cellular emigration from the leading edge of explants. Microinjected probes (Fab' anti-FN, Fab' anti-integrin and RGD-peptides) that disrupt cell adhesion to the FN-matrix on basal surface of the blastocoel roof also disrupt normal anuran gastrulation, producing blocked embryos with no adhesion of leading edge mesodermal cells to the blastocoel roof, abnormal epiboly, and defects of mesodermal cell spreading across the basal surface of the blastocoel roof toward the animal pole. These results show that the FN-rich fibrillar extracellular matrix on the basal surface of the blastocoel roof is required for normal gastrulation in Rana pipiens embryos.

Animals↗
PubMed1993

Ectoderm promotes differentiation of the presumptive ventral mesoderm in early gastrulae of Bufo arenarum.

Cultures of both isolated and conjugated explants from early gastrulae of Bufo arenarum were prepared for a study of the development of ventral mesoderm. Only combinations including components of the deep ventral marginal zone and the animal pole successfully differentiated into blood cells (erythrocytes). Histological studies indicated that, while prospective mesodermal cells constituted the only source of such cells, prospective ectodermal cells provided the necessary stimulus for this kind of differentiation. Differentiated cultures, in which the tracer of cell-lineage fluorescein dextran amine was used to label these components, confirmed the above conclusions. These findings are discussed in the context of current concepts about the formation of mesoderm.

Animals↗
PubMed2004

Developmental fate of the mandibular mesoderm in the lamprey, Lethenteron japonicum: Comparative morphology and development of the gnathostome jaw with special reference to the nature of the trabecula cranii.

The vertebrate jaw is a mandibular-arch derivative, and is regarded as the synapomorphy that defines the gnathostomes. Previous studies (Kuratani et al., Phil. Trans. Roy. Soc. 356:15, 2001; Shigetani et al., Science 296:1319, 2002) have suggested that the oral apparatus of the lamprey is derived from both the mandibular and premandibular regions, and that the jaw has arisen as a secondary narrowing of the oral patterning mechanism into the mandibular-arch domain. The heterotopy theory of jaw evolution states that the lamprey upper lip is a premandibular element, leaving further questions unanswered as to the homology of the trabecula in the lamprey and gnathostomes, and to the morphological nature of the muscles in the upper lip. Using focal injection of vital dyes into the cheek process core of lamprey embryos, we found that the upper lip muscle and trabecula are both derived from mandibular mesoderm. Secondary movement of the muscle primordium is also evident when the expression of the early muscle marker gene, LjMA2, is visualized. A nerve-fiber labeling study revealed that the upper lip muscle-innervating neurons are located in the rostral part of the brain stem, where the trigeminal motor nuclei are not found in gnathostomes. We conclude that the lamprey upper lip is composed of premandibular ectomesenchyme and a lamprey-specific muscle component derived from the mandibular mesoderm innervated by lamprey-specific motoneurons. Furthermore, the lamprey trabecula is most likely equivalent to a mesodermally derived neurocranial element, similar to the parachordal element in gnathostomes, rather than to the neural-crest-derived prechordal element.

Animals↗
PubMed1996

Retinoic acid promotes neural and represses mesodermal gene expression in mouse embryonic stem cells in culture.

Mouse embryonic stem cells treated with retinoic acid are induced to differentiate into neuron-like cells (Bain et al. (1995) Dev. Biol. 168, 342-357). Here we have examined the expression of a set of neural- and mesoderm-specific genes during this in vitro differentiation process. mRNAs encoding the neural genes Wnt-1, MASH1, the light and medium isoforms of neurofilaments, and the neurotransmitter-synthesizing enzyme glutamic acid decarboxylase are all strongly upregulated by retinoic acid treatment; expression of these genes occurs in a temporal pattern resembling that in the developing brain. In contrast, retinoic acid blocks the expression of the mesodermal genes Brachyury, cardiac actin, and zeta-globin. Thus, retinoic acid exerts both pro-neuronal and anti-mesodermal activities on mouse embryonic stem cells in culture.

Animals↗
PubMed1997

Mesoderm induction by BMP-4 and -7 heterodimers.

Bone morphogenetic proteins (BMPs) are peptide growth factors belonging to the TGF-beta superfamily. A large number of these ligands, including BMP-2, -4 and -7 is expressed during early embryogenesis in the vertebrate embryo. In this study, we demonstrate that BMP-7 has ventralizing activity both in ectodermal explants as well as in whole embryos. As it was the case for BMP-2 and BMP-4, BMP-7 is a very poor inducer when provided as a homodimer protein. Because of this weak mesoderm inducing activity, it has been suggested that mesoderm induction by BMPs might represent an artifact of overexpression. We provide evidence demonstrating that unlike the homodimers of BMP-4 or BMP-7, the purified recombinant heterodimer of Xenopus BMP-4 and BMP-7 (BMP-4/7) has a potent mesoderm inducing activity at physiological concentrations. These results provide the first evidence for an embryonic function of BMP-4/7 heterodimers in the vertebrate embryo.

Animals↗
PubMed1994

Superficial cells in the early gastrula of Rana pipiens contribute to mesodermal derivatives.

We have studied the fate of presumptive mesodermal cells in the early Rana pipiens gastrula. We labeled superficial cells of the early gastrula with 125I. We also labeled all cells in a gastrula with rhodamine-lysine-dextran cell lineage tracer and superficial cells with 125I and then grafted small pieces of the marginal zone orthotopically into unlabeled host embryos. Labeled progeny were identified in sectioned embryos at the tail bud stage. The use of double-labeled grafts allowed us to study the relative contributions by superficial and deep cells to different derivatives. We found that the notochord and somite regions are both derived from the superficial and deep portions of circumblastoporal regions. In contrast, pronephros, lateral plate, cardiac anlagen, and blood cells only arise from deep cells in circumblastoporal regions. Such observations indicate that the fate map for R. pipiens is different from that of Xenopus laevis, where mesodermal derivatives appear to be restricted to the deep layers, and from that of Pleurodeles waltl, where all mesodermal derivatives are formed both from superficial and deep layers. We also have shown that from the neurula stage there is substantial mixing between cells due to the ingression of cells in the dorsal region so that superficial labeled cells, initially located in the roof of the archenteron, contribute to ventral regions of both the somites and notochord.

Animals↗
PubMed1994

Expression patterns of Hoxb genes in the Xenopus embryo suggest roles in anteroposterior specification of the hindbrain and in dorsoventral patterning of the mesoderm.

Hox genes are thought to participate in patterning the anteroposterior (a-p) axis during vertebrate embryogenesis. In this investigation, the spatial expression of six Hoxb genes was analyzed in early embryos of Xenopus laevis by in situ hybridization. Hoxb gene expression was first detected in late gastrulae/early neurulae, by which stage, the characteristic spatially colinear Hoxb gene expression sequence was already apparent. Dissection experiments indicated that the establishment of these localized expression patterns coincides with the acquisition of anteroposterior positional information along the main body axis. The Hoxb genes continued to be expressed in similar domains along the anteroposterior axis at all developmental stages examined, although there were some changes in expression at the cellular level. Interestingly, the 3' genes, Hoxb-1, Hoxb-3, and Hoxb-4 were expressed in very restricted domains in the future hindbrain, while Hoxb-5, Hoxb-7, and Hoxb-9 transcripts were present along the entire presumptive spinal cord. It was thus notable that the 5' Hoxb genes exhibited different types of expression domain than the 3' Hoxb genes. These observations suggest that there may be different mechanisms regulating the expression of the 3' and 5' Hoxb genes. Expression of all of the Hoxb genes analyzed, except Hoxb-4, was predominantly detectable in the central nervous system or in neural crest-derived structures. Hoxb-4 mRNA was detected in the central nervous system, but interestingly, the major expression site for this gene was the somites. The other Hoxb genes tested failed to show significant expression in the somitic mesoderm, although transcripts from genes 5' from Hoxb-4 were detected in other mesodermal tissues. In the vertebrate trunk, anteroposterior patterning of the CNS is thought to be regulated by the somites. The results obtained here for Xenopus embryos did not explicitly support the idea of a Hoxb code for the somites, although we cannot rule this out. Instead, interestingly, the data were consistent with a role for Hoxb genes in dorsoventral patterning of the mesoderm.

Animals↗
PubMed1995

Activin and its receptors during gastrulation and the later phases of mesoderm development in the chick embryo.

We have cloned chick homologues of the type-II activin receptor, which we have designated cActR-IIA and -IIB. Binding assays show that the two receptors are indistinguishable in their ability to bind activin-A, with comparable kds. Injection of mRNAs encoding these receptors into Xenopus embryos causes axial duplications. Expression of both receptors can first be detected in the primitive streak by in situ hybridization. This suggests that these genes may be activated in response to mesoderm induction. In agreement with this, we find that treatment of preprimitive streak chick embryos with activin-A leads to rapid induction of the expression of cActR-IIB. At later stages, cActR-IIA transcripts become localized mainly in the notochord and myotome and cActR-IIB in the dorsal neural tube, proximal-anterior part of the limb bud, sensory placodes, and specific regions of the fore- and midbrain. To test the response of early chick embryonic tissues to activin, we designed a new in vitro assay for differentiation. We find that explants of area opaca epiblast or posterior primitive streak from various stages can respond to activin treatment by differentiating into a variety of mesodermal cell types in a dose-dependent manner. These results suggest that the importance of activin-related signaling pathways is not confined to pregastrulation stages and that these receptors may be involved in mediating the effects of inducing signals during later stages of development of the mesoderm, limbs, and nervous system.

Activin Receptors↗
PubMed1995

FGF can induce outgrowth of somatic mesoderm both inside and outside of limb-forming regions.

In the vertebrate embryo, only somatopleural cells in the limb-forming region are released from the mesodermal layer and undergo outgrowth from the embryonic body to form the limb bud. Molecular signals which regulate limb bud induction are unknown to date. In the present study we examined the ability of fibroblast growth factor (FGF) to induce limb bud formation in chicken embryos. A replication-defective retrovirus encoding FGF type 4 with a reporter, bacterial beta-galactosidase, was microinjected into lateral plate mesoderm inside and outside limb-forming regions. Effects of the ectopic and precocious expression of FGF were assessed at various stages after infection. Here we report that somatic mesodermal cells in both flanks and limb-forming regions can respond to FGF and induce limb bud-like outgrowth. The supernumerary limb bud induced within a limb-forming region differentiated into extralimb structures. These results strongly suggest potential roles of FGF signaling for induction of limb bud formation.

Animals↗
PubMed1995

Integrin alpha v subunit is expressed on mesodermal cell surfaces during amphibian gastrulation.

Mesodermal cell migration during amphibian gastrulation is dependent on cellular interactions with fibronectin. One mechanism whereby cells bind fibronectin is through alpha v-containing integrin heterodimers. In order to investigate the role of alpha v in amphibian gastrulation, we have cloned the Pleurodeles homologue of the integrin alpha v subunit using homology PCR. The deduced amino acid sequence is 73 and 74% identical with the human and chick homologues, respectively. The 4.8-kb mRNA is expressed during oogenesis and persists throughout development. Messenger RNA and protein are widely expressed in oocytes and embryos while cell surface expression is spatially regulated. The protein first appears on the plasma membrane of fully grown oocytes. Fertilization results in the progressive loss of alpha v membrane localization. Before and during gastrulation, the integrin alpha v subunit is expressed on the surface of mesodermal cells. These data show that alpha v expression is developmentally regulated by a post-translational mechanism which correlates with the onset of mesodermal cell migration at gastrulation.

Amino Acid Sequence↗
PubMed1996

Induction of axial mesoderm by zDVR-1, the zebrafish orthologue of Xenopus Vg1.

The zebrafish DVR-1 (zDVR-1) gene, like Xenopus Vg1, is present maternally as an unprocessed precursor protein which is distributed ubiquitously along the future dorsoventral axis. Also, like Vg1, overexpression of zDVR-1 in zebrafish directs synthesis of more precursor, but no processed protein. However, the native zDVR-1 precursor is processed to mature protein when expressed in Xenopus. Like processed Vg1, mature zDVR-1 is a potent inducer of axial mesoderm. The parallels in expression pattern, apparent regulation of protein processing, and mesoderm-inducing activity support the hypothesis that localized protein processing controls production of a dorsal mesoderm inducer in these two species. Furthermore, using mutant mRNAs, we show that cleavage site sequences of the precursor protein are important in regulating protein processing.

Amino Acid Sequence↗
PubMed1996

Wingless signaling induces nautilus expression in the ventral mesoderm of the Drosophila embryo.

The segregation of founder cells from the somatic mesoderm is a prerequisite for the formation of body wall muscles in the Drosophila embryo. The myogenic basic helix-loop-helix protein, Nautilus (Nau), is expressed in a subset of these founder cells in medial and lateral positions in the somatic mesoderm. Mutations in the wingless (wg) gene, which encodes a secreted growth factor, lead to the complete loss of Nau-expressing medial muscle precursor cell clusters, but not lateral clusters. Using the GAL4/UAS system, we demonstrate that the wg-derived signal can originate from either ectoderm or mesoderm to influence nau expression. By using a temperature-sensitive wg allele, we also show that wg function is required during and after gastrulation for the formation of Nau-expressing medial muscle precursor cell clusters. Our results, combined with recent studies from chick, suggest a conserved role for Wg signaling pathways during muscle development.

Alleles↗
PubMed1997

Mesodermal guidance of pioneer axon growth.

Pioneer axons in insect legs are experimentally accessible model systems for the molecular identification and cellular localization of guidance cues regulating the path of axon growth. A detailed study of the Fe2 pioneer axons in the legs of the cockroach was performed to examine the diversity of guidance mechanisms. A detailed microscopic analysis of the axons at various points in their trajectory indicates that the Fe2 axons grow on a mesodermal substratum which contains the cues guiding their growth along a stereotyped path. An identified pair of muscle pioneer cells (MPC) are likely to play an important role in enabling the Fe2 growth cones to respond to mesodermal guidance cues. The addition of heparan sulfate, heparitinase, and phosphatidylinositol-specific phospholipase C to the medium perturbs the in situ path of growth of the Fe2 axons and the location of the MPC in cultured embryos. This indicates a role for heparan sulfate proteoglycans and glycosylphosphatidylinositol-anchored proteins in axon guidance. When these results are compared to those of similar experiments performed on the well-characterized Ti1 axons, they indicate significant differences in the mechanisms that are used for axon guidance. The Fe2 neurons are a good model for elucidating the mechanisms used to guide axon growth on nonmuscle mesodermal substrates often encountered in the periphery of vertebrate embryos.

Animals↗
PubMed1998

Protein tyrosine kinase activity following fertilization is required to complete gastrulation, but not for initial differentiation of endoderm and mesoderm in the sea urchin embryo.

The egg activation process functions to implement developmental programs that act much later in embryogenesis. One example of this is the fact that application of protein tyrosine kinase inhibitors to the fertilized sea urchin egg for a 15-min period results in a defect in the gastrulation process occurring over 24 h later (Kinsey, W. H., Dev. Biol. 172, 704-707, 1995). In the present study, we show that the window of sensitivity is not due to differential uptake of inhibitor, and establish that the inhibitor inhibits tyrosine kinase activity at the time of application. We also demonstrate that inhibition of protein tyrosine kinase activity in the zygote causes a specific defect in the morphogenetic movements associated with gastrulation without interfering with the initial specification and differentiation of endoderm and mesoderm. Differentiation events occurring concurrent with or subsequent to gastrulation were also suppressed in embryos derived from treated zygotes. These findings indicate that fertilization initiates a signaling cascade involving protein tyrosine kinase activity that is required specifically for events at gastrulation. This signaling event is required to complete the developmental program of both endoderm and mesoderm, but is different from those events necessary for initial specification of endodermal and mesodermal cell fate.

Animals↗
PubMed1998

Hedgehog and wingless induce metameric pattern in the Drosophila visceral mesoderm.

The Drosophila visceral mesoderm (VM) is a favorite system for studying the regulation of target genes by Hox proteins. The VM is formed by cells from only the anterior subdivision of each mesodermal parasegment (PS). We show here that the VM itself acquires modular anterior-posterior subdivisions similar to those found in the ectoderm. As VM progenitors merge to form a continuous band running anterior to posterior along the embryo, expression of connectin (con) in 11 metameric patches within the VM reveals VM subdivisions analagous to ectodermal compartments. The VM subdivisions form in response to ectodermal production of secreted signals encoded by the segment polarity genes hedgehog (hh) and wingless (wg) and are independent of Hox gene activity. A cascade of induction from ectoderm to mesoderm to endoderm thus subdivides the gut tissues along the A-P axis. Induction of VM subdivisions may converge with Hox-mediated information to refine spatial patterning in the VM. Con patches align with ectodermal engrailed stripes, so the VM subdivisions correspond to PS 2-12 boundaries in the VM. The PS boundaries demarcated by Con in the VM can be used to map expression domains of Hox genes and their targets with high resolution. The resultant map suggests a model for the origins of VM-specific Hox expression in which Hox domains clonally inherited from blastoderm ancestors are modified by diffusible signals acting on VM-specific enhancers.

Animals↗
PubMed1999

A novel BMP expressed in developing mouse limb, spinal cord, and tail bud is a potent mesoderm inducer in Xenopus embryos.

The bone morphogenetic proteins (BMPs) play critical roles in patterning the early embryo and in the development of many organs and tissues. We have identified a new member of this multifunctional gene family, BMP-11, which is most closely related to GDF-8/myostatin. During mouse embryogenesis, BMP-11 is first detected at 9.5 dpc in the tail bud with expression becoming stronger as development proceeds. At 10.0 dpc, BMP-11 is expressed in the distal and posterior region of the limb bud and later localizes to the mesenchyme between the skeletal elements. BMP-11 is also expressed in the developing nervous system, in the dorsal root ganglia, and dorsal lateral region of the spinal cord. To assess the biological activity of BMP-11, we tested the protein in the Xenopus ectodermal explant (animal cap) assay. BMP-11 induced axial mesodermal tissue (muscle and notochord) in a dose-dependent fashion. At higher concentrations, BMP-11 also induced neural tissue. Interestingly, the activin antagonist, follistatin, but not noggin, an antagonist of BMPs 2 and 4, inhibited BMP-11 activity on animal caps. Our data suggest that in Xenopus embryos, BMP-11 acts more like activin, inducing dorsal mesoderm and neural tissue, and less like other family members such as BMPs 2, 4, and 7, which are ventralizing and anti-neuralizing signals. Taken together, these data suggest that during vertebrate embryogenesis, BMP-11 plays a unique role in patterning both mesodermal and neural tissues.

Amino Acid Sequence↗
PubMed1999

Murine fibroblast growth factor receptor 1alpha isoforms mediate node regression and are essential for posterior mesoderm development.

Alternative splicing in the fibroblast growth factor receptor 1 (Fgfr1) locus generates a variety of splicing isoforms, including FGFR1alpha isoforms, which contain three immunoglobulin-like loops in the extracellular domain of the receptor. It has been previously shown that embryos carrying targeted disruptions of all major isoforms die during gastrulation, displaying severe growth retardation and defective mesodermal structures. Here we selectively disrupted the FGFR1alpha isoforms and found that they play an essential role in posterior mesoderm formation during gastrulation. We show that the mutant embryos lack caudal somites, develop spina bifida, and die at 9.5-12.5 days of embryonic development because they are unable to establish embryonic circulation. The primary defect is a failure of axial mesoderm cell migration toward the posterior portions of the embryos during gastrulation, as revealed by regional marker analysis and DiI labeling. In contrast, the anterior migration of the notochord is unaffected and the embryonic structures rostral to the forelimb are relatively normal. These data demonstrate that FGF/FGFR1alpha signals are posteriorizing factors that control node regression and posterior embryonic development.

Abnormalities, Multiple↗
PubMed1999

Expression of Pax-3 in the lateral neural plate is dependent on a Wnt-mediated signal from posterior nonaxial mesoderm.

During early patterning of the vertebrate neuraxis, the expression of the paired-domain transcription factor Pax-3 is induced in the lateral portions of the posterior neural plate via posteriorizing signals emanating from the late organizer and posterior nonaxial mesoderm. Using a dominant-negative approach, we show in explant assays that Pax-3 inductive activities from the organizer do not depend on FGF, retinoic acid, or XWnt-8, either alone or in combination, suggesting that the organizer may produce an unknown posteriorizing factor. However, Pax-3 inductive signals from posterior nonaxial mesoderm are Wnt-dependent. We show that Pax-3 expression in the lateral neural plate expands in XWnt-8-injected embryos and is blocked by dominant-negative XWnt-8. Similarly, we show that the homeodomain transcription factor Msx-1, which like Pax-3 is an early marker of the lateral neural plate, is induced by posterior nonaxial mesoderm and blocked by dominant-negative XWnt-8. Finally, we show that Rohon-Beard primary neurons, a cell type that develops within the lateral neural plate, are also blocked in vivo by dominant-negative Xwnt-8. Together these data support a model in which patterning of the lateral neural plate by Wnt-mediated signals is an early event that establishes a posteriolateral domain, marked by Pax-3 and Msx-1 expression, from which Rohon-Beard cells and neural crest will subsequently arise.

Animals↗