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At least 685 records · Page 38Linked to original sources
PubMed2003

A new view of patterning domains in the vertebrate mesoderm.

The musculoskeletal system of vertebrates is derived from the embryonic mesoderm. Its structures are categorized as epaxial or hypaxial based on their adult position and innervation. The epaxial/hypaxial terminology is also used to describe regions of the embryonic somites based on fate mapping of somitic derivatives. However, the adult, functional distinctions are not fully consistent with the changing embryonic environments of mesodermal populations during morphogenesis, and the traditional terminology loses accuracy when used to describe certain mutant phenotypes. Here we describe a new terminology naming two mesodermal environments defined by the lineage of the included cells. We discuss how mutant phenotypes may be better explained by consideration of the embryonic context in which genes take their effect and argue that the recognition of these embryonic territories clarifies description and discussion of the morphogenesis and patterning of the musculoskeletal system.

Animals↗
PubMed2003

A Tcf4-positive mesodermal population provides a prepattern for vertebrate limb muscle patterning.

Nai;ve myogenic cells migrate from the somites into the developing vertebrate limb, where they simultaneously differentiate into myotubes and form distinct anatomical muscles. Limb signals have been hypothesized to direct the pattern of muscles formed, but the molecular nature of these signals and the identity of the cells that produce them have remained unclear. We have identified a population of lateral plate-derived limb mesodermal cells in both chick and mouse that expresses the transcription factor Tcf4 in a muscle-specific pattern independently of the muscle cells themselves. Functional experiments in the chick demonstrate that TCF4 and the Wnt-beta-catenin pathway in these limb mesodermal cells are critical for muscle patterning. We propose that Tcf4-expressing cells establish a prepattern in the limb mesoderm that determines the sites of myogenic differentiation and thus establishes the basic pattern of limb muscles.

Animals↗
PubMed2003

Differential mesodermal expression of two amphioxus MyoD family members (AmphiMRF1 and AmphiMRF2).

To explore the evolution of myogenic regulatory factors in chordates, we isolated two MyoD family genes (AmphiMRF1 and AmphiMRF2) from amphioxus. AmphiMRF1 is first expressed at the late gastrula in the paraxial mesoderm. As the first somites form, expression is restricted to their myotomal region. In the early larva, expression is strongest in the most anterior and most posterior somites. AmphiMRF2 transcription begins at mid/late gastrula in the paraxial mesoderm, but never spreads into its most anterior region. Through much of the neurula stage, AmphiMRF2 expression is strong in the myotomal region of all somites except the most anterior pair; by late neurula expression is downregulated except in the most posterior somites forming just rostral to the tail bud. These two MRF genes of amphioxus have partly overlapping patterns of mesodermal expression and evidently duplicated independent of the diversification of the vertebrate MRF family.

Animals↗
PubMedDate not supplied

Cell-autonomous action of zebrafish spt-1 mutation in specific mesodermal precursors.

In zebrafish, as in Xenopus, the well-orchestrated cell movements of gastrulation can be dissected into several components, including epiboly, involution, convergence and extension. Embryos homozygous for the recessive lethal mutation spt-1(b104) or 'spadetail' have a complex set of defects in the trunk of the embryo that may arise secondarily after loss of one of these movements, convergence, from those precursors that would normally have given rise to trunk somitic mesoderm. We have now tested this hypothesis by transplanting cells between wild-type and mutant embryos, to identify the cells that spt-1 affects directly. Our results show that the mutation autonomously affects only those mesodermal precursors located along the lateral margin of the early gastrula blastoderm. Other mesodermal cells and all ectodermal precursors seem not to require function of the wild-type gene. Our findings reveal an unexpectedly delicate genetic control of vertebrate gastrulation.

Animals↗
PubMed2004

Antero-posterior tissue polarity links mesoderm convergent extension to axial patterning.

Remodelling its shape, or morphogenesis, is a fundamental property of living tissue. It underlies much of embryonic development and numerous pathologies. Convergent extension (CE) of the axial mesoderm of vertebrates is an intensively studied model for morphogenetic processes that rely on cell rearrangement. It involves the intercalation of polarized cells perpendicular to the antero-posterior (AP) axis, which narrows and lengthens the tissue. Several genes have been identified that regulate cell behaviour underlying CE in zebrafish and Xenopus. Many of these are homologues of genes that control epithelial planar cell polarity in Drosophila. However, elongation of axial mesoderm must be also coordinated with the pattern of AP tissue specification to generate a normal larval morphology. At present, the long-range control that orients CE with respect to embryonic axes is not understood. Here we show that the chordamesoderm of Xenopus possesses an intrinsic AP polarity that is necessary for CE, functions in parallel to Wnt/planar cell polarity signalling, and determines the direction of tissue elongation. The mechanism that establishes AP polarity involves graded activin-like signalling and directly links mesoderm AP patterning to CE.

Activins↗
PubMed1994

Polysialic acid of the neural cell adhesion molecule (N-CAM) is widely expressed during organogenesis in mesodermal and endodermal derivatives.

We have studied the expression of homopolymers of alpha 2,8-linked sialic acid (polySia) and the neural cell adhesion molecule (N-CAM) during the embryonic and fetal development of rat, chicken and man using immunocytochemistry and immunoblotting. During development, polySia and N-CAM were widely expressed in mesodermally and neuro-ectodermally derived elements. In specific developmental processes, cells of endodermal and ectodermal (non-neural) origin were also immunoreactive for these molecules. Loss of polySia and N-CAM immunoreactivity often accompanied differentiation of mesodermally derived cells. In cartilage formation for instance, cells in precartilaginous mesenchymal condensations stained for N-CAM and polySia until the first appearance of specific chondrocyte function, independent of the stage of development. Transient de novo expression of polySia, in newly induced ectodermal cells, paralleled the reciprocal inductive interactions of mesodermally derived cells with cells of ectodermal origin during hair follicle formation. All ectodermally derived hair follicle cells, except the putative stem cells, later ceased expression of these molecules. Ectodermal expression of polySia and N-CAM was otherwise rare. The endodermally derived epithelium of the digestive and respiratory tracts were polySia and N-CAM immunoreactive early in organogenesis (embryonic day 12 in mouse). Cells of this derivation later all became unreactive, although decrease in immunoreactivity during development was faster in derivatives of more cranial portions of the endoderm. In general, during organogenesis, epithelial elements showed polySia and N-CAM expression before and during epithelium formation, thereafter losing immunoreactivity, irrespective of the developmental origin of the epithelial cells. PolySia and N-CAM staining in the chicken respiratory tract epithelium was more wide-spread and lasted significantly longer than in either man or rat. Cells that expressed N-CAM, but not polySia, were found during the development of both skin and pancreas, indicating independent control of polySia expression. Outside the nervous system no cells that expressed polySia but not N-CAM were observed.

Animals↗
PubMed2001

Immunocytochemical analysis of vimentin expression patterns in porcine embryos suggests mesodermal differentiation from day 9 after conception.

The expression of the intermediate filament proteins vimentin and keratin in porcine embryos was studied by whole-mount immunocytochemistry between day 7 and day 11 after conception. Expression of vimentin was first detected in the inner cell mass of about 50% of the 9-day-old embryos. In elongated 11-day-old embryos, cells expressing vimentin were observed in the epiblast (after disappearance of Rauber's membrane) and in cells migrating from the epiblast between the trophoblast and the underlying hypoblast layer. A keratin-positive response was observed in trophectoderm cells at all stages. These findings suggest that inner cell mass cells in the pig start differentiating into mesodermal cells not later than day 9 after conception. While the delamination of the mesodermal germ layer is known to correlate with the loss of pluripotency of the inner cell mass cells, the early onset of mesodermal differentiation in the porcine embryo, characterized by vimentin expression and in contrast to the mouse, could in part be responsible for the lack of success in establishing pluripotent embryonic stem cell lines in this species. Our results suggest that further attempts to isolate inner cell mass-derived pluripotent cells should be attempted well before day 9 after conception.

Animals↗
PubMed2002

Antisense inhibition of Xbrachyury impairs mesoderm formation in Xenopus embryos.

Expression of the Xbrachyury (Xbra) gene was inhibited by antisense RNA synthesized in situ from an expression vector read by RNA polymerase III, injected into the fertilized egg or the 2-cell stage embryo of Xenopus laevis. Antisense-treated embryos had markedly reduced levels of Xbra mRNA and protein, and showed deficiencies in mesodermal derivatives and axis formation. In particular, organization of the posterior axis was affected, but often the anterior axis was also reduced. Some embryos failed to form mesoderm altogether and remained amorphous. The antisense effect is dose-dependent and may be "rescued" by overexpression of Xbra. In Xbra-deficient embryos, expression of several mesodermal genes (Xvent, pintallavis, Xlim, Xwnt-8 and noggin) was reduced to varying degrees, whereas goosecoid levels remained normal. The modified expression levels were partly normalized when Xbra deficiency was rescued. The observation that antisense inhibition yields slightly different phenotypes from dominant-negative inhibition suggests the recommendation of using several surrogate genetic approaches to determine the functional role of a gene in Xenopus development.

Animals↗
PubMed1973

Control of chondrogenic expression in mesodermal cells of embryonic chick limb.

Chick-limb mesodermal cells have been maintained in tissue culture under conditions that permit development of muscle and cartilage. 3-Acetylpyridine, a nicotinamide-antagonized muscle teratogen, potentiates chondrogenic expression in cell cultures, as evidenced by histological and biochemical criteria, including the production of chondromucoprotein. Xylosyltransferase and N-acetylgalactosaminyltransferase are two enzymes required for chondromucoprotein synthesis; the specific activities of these enzymes were measured in differentiating mesodermal cells cultured for various periods of time in the presence and absence of 3-acetylpyridine and in intact limb tissue. The ratios of specific enzyme activities were nearly the same in both cultured cells and limb tissue, although the levels of both transferases increased severalfold during chondrogenic expression by mesodermal cells in culture. 3-Acetylpyridine causes the specific activities of xylosyl- and N-acetylgalactosaminyltransferases to increase 10- and 2-fold, respectively, above those of untreated cultures. Compared to the ratio of transferase activities in limb tissue and differentiating cell cultures, 3-acetylpyridine appears to increase the activity of xylosyltransferase, the initiator of chondroitin sulfate chain synthesis, more than does N-acetylgalactosaminyltransferase; this finding implies that the synthesis of these two enzymes may be separately regulated.

Animals↗
PubMed1991

Widespread expression of MyoD genes in Xenopus embryos is amplified in presumptive muscle as a delayed response to mesoderm induction.

The MyoD gene codes for an important regulatory factor in skeletal myogenesis. To explore the relationship between mesoderm induction in Xenopus embryos and expression of MyoD, I have monitored MyoD mRNA levels in normal embryos and cultured explants by RNase protection. Transcription from the two Xenopus MyoD gene copies is activated weakly across the whole embryo at the midblastula transition, and this activation occurs in the absence of mesoderm induction. In response to induction this basal expression is amplified 50- to 100-fold, but in animal-pole explants 6-10 hr elapse before induced mRNAs appear, and this induction requires prior protein synthesis. The promiscuous transcripts disappear from animal explants at a time when induction "competence" is lost, suggesting a link between these events. The data highlight a broad, but transient, permissiveness for MyoD expression in embryos, which is propagated and amplified only in presumptive muscle in response to induction. Moreover, muscle-specific MyoD expression is a relatively late (postgastrulation) event in the mesoderm-induction cascade.

Actins↗
PubMed1993

Loss of function of the Drosophila zfh-1 gene results in abnormal development of mesodermally derived tissues.

The Drosophila zfh-1 gene encodes an unusual protein with nine Cys2His2 type zinc-finger motifs and one homeodomain that shows a complex pattern of expression in the embryonic mesoderm and nervous system. To study the function of zfh-1, we generated loss-of-function zfh-1 mutations. Phenotypic analysis of zfh-1 mutant embryos reveals that the gene is not required for the initial segregation of the mesoderm or for the differentiation of mesodermally derived tissues. Rather, loss of zfh-1 function results in various degrees of local errors in cell fate or positioning.

Alleles↗
PubMed1994

D-MEF2: a MADS box transcription factor expressed in differentiating mesoderm and muscle cell lineages during Drosophila embryogenesis.

The myocyte enhancer factor (MEF) 2 family of transcription factors has been implicated in the regulation of muscle transcription in vertebrates. We have cloned a protein from Drosophila, termed D-MEF2, that shares extensive amino acid homology with the MADS (MCM1, Agamous, Deficiens, and serum-response factor) domains of the vertebrate MEF2 proteins. D-mef2 gene expression is first detected during Drosophila embryogenesis within mesodermal precursor cells prior to specification of the somatic and visceral muscle lineages. Expression of D-mef2 is dependent on the mesodermal determinants twist and snail but independent of the homeobox-containing gene tinman, which is required for visceral muscle and heart development. D-mef2 expression precedes that of the MyoD homologue, nautilus, and, in contrast to nautilus, D-mef2 appears to be expressed in all somatic and visceral muscle cell precursors. Its temporal and spatial expression patterns suggest that D-mef2 may play an important role in commitment of mesoderm to myogenic lineages.

Amino Acid Sequence↗
PubMed1995

Meso1, a basic-helix-loop-helix protein involved in mammalian presomitic mesoderm development.

To identify genes involved in the regulation of early mammalian development, we have developed a dominant-negative mutant basic-helix-loop-helix (bHLH) protein probe for interaction cloning and have isolated a member of the bHLH family of transcription factors, Meso1. Meso1-E2A heterodimers are capable of binding to oligonucleotide probes that contain a bHLH DNA recognition motif. In mouse embryos, Meso1 is expressed prior to MyoD1 family members. Meso1 expression is first detected at the neural plate stage of development in the paraxial mesoderm of the head and in presomitic mesodermal cells prior to their condensation into somites. Our findings suggest that Meso1 may be a key regulatory gene involved in the early events of vertebrate mesoderm differentiation.

Amino Acid Sequence↗
PubMed1998

Failure of egg cylinder elongation and mesoderm induction in mouse embryos lacking the tumor suppressor smad2.

smad genes constitute a family of nine members whose products serve as intracellular mediators of transforming growth factor beta signals. SMAD2, which is a tumor suppressor involved in colorectal and lung cancer, has been shown to induce dorsal mesoderm in Xenopus laevis in response to transforming growth factor beta and activins. The smad2 gene is expressed ubiquitously during murine embryogenesis and in many adult mouse tissues. Animals that lacked smad2 died before 8.5 days of development (E8.5). E6.5 homozygous mutants were smaller than controls, lacked the extraembryonic portion of the egg cylinder, and appeared strikingly similar to E6.5 smad4 mutants. This similarity was no longer evident at E7.5, however, because the smad2 mutants contained embryonic ectoderm within their interiors. Molecular analysis showed that smad2 mutant embryos did not undergo gastrulation or make mesoderm. The results demonstrate that smad2 is required for egg cylinder elongation, gastrulation, and mesoderm induction.

Animals↗
PubMed1998

The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice.

Members of the transforming growth factor (TGF)-beta superfamily have been shown to play a variety of important roles in embryogenesis, including dorsal and ventral mesoderm induction. The tumor suppressor SMAD4, also known as DPC4, is believed to be an essential factor that mediates TGF-beta signals. To explore functions of SMAD4 in development, we have mutated it by truncating its functional C-domain. We show that Smad4 is expressed ubiquitously during murine embryogenesis. Mice heterozygous for the Smad4(ex8/+) mutation are developmentally normal, whereas homozygotes die between embryonic day 6.5 (E6.5) and 8.5. All Smad4(ex8/ex8) mutants are developmentally delayed at E6 and show little or no elongation in the extraembryonic portion of late egg cylinder stage embryos. Consistent with this, cultured Smad4(ex8/ex8) blastocyst outgrowths suffer cellular proliferation defects and fail to undergo endoderm differentiation. Although a portion of mutant embryos at E8.5 show an increase in the embryonic ectoderm and endoderm, morphological and molecular analyses indicate that they do not form mesoderm. Altogether, these data demonstrate that SMAD4-mediated signals are required for epiblast proliferation, egg cylinder formation, and mesoderm induction.

Animals↗
PubMed2000

Participation of transcription elongation factor XSII-K1 in mesoderm-derived tissue development in Xenopus laevis.

We isolated a cDNA clone for a novel member of the S-II family of transcription elongation factors from Xenopus laevis. This S-II, named XSII-K1, is assumed to be the Xenopus homologue of mouse SII-K1 that we reported previously (Taira, Y., Kubo, T., and Natori, S. (1998) Genes Cells 3, 289-296). Expression of the XSII-K1 gene was found to be restricted to mesoderm-derived tissues such as liver, kidney, and skeletal muscle. Contrary to the general S-II gene, expression of the XSII-K1 gene was not detected in embryos at stages earlier than 11. The animal cap assay revealed that activin A, but not basic fibroblast growth factor, induced expression of the XSII-K1 gene and that it participated in the expression of mesoderm-specific genes such as Xbra and Xalpha-actin. This is the first demonstration that the regulation at the level of transcription elongation is included in the development of mesoderm-derived tissues.

Actins↗
PubMed2002

Increased basal cAMP-dependent protein kinase activity inhibits the formation of mesoderm-derived structures in the developing mouse embryo.

A targeted disruption of the RIalpha isoform of protein kinase A (PKA) was created by using homologous recombination in embryonic stem cells. Unlike the other regulatory and catalytic subunits of PKA, RIalpha is the only isoform that is essential for early embryonic development. RIalpha homozygous mutant embryos fail to develop a functional heart tube at E8.5 and are resorbed at approximately E10.5. Mutant embryos show significant growth retardation and developmental delay compared with wild type littermates from E7.5 to E10.5. The anterior-posterior axis of RIalpha mutants is well developed, with a prominent head structure but a reduced trunk. PKA activity measurements reveal an increased basal PKA activity in these embryos. Brachyury mRNA expression in the primitive streak of RIalpha mutants is significantly reduced, consistent with later deficits in axial, paraxial, and lateral plate mesodermal derivatives. This defect in the production and migration of mesoderm can be completely rescued by crossing RIalpha mutants to mice carrying a targeted disruption in the Calpha catalytic subunit, demonstrating that unregulated PKA activity rather than a specific loss of RIalpha is responsible for the phenotype. Primary embryonic fibroblasts from RIalpha mutant embryos display an abnormal cytoskeleton and an altered ability to migrate in cell culture. Our results demonstrate that unregulated PKA activity negatively affects growth factor-mediated mesoderm formation during early mouse development.

Amino Acid Sequence↗
PubMed2005

Overexpression of Nodal promotes differentiation of mouse embryonic stem cells into mesoderm and endoderm at the expense of neuroectoderm formation.

Understanding how to direct the fate of embryonic stem (ES) cells upon differentiation is critical to their eventual use in therapeutic applications. Clues for controlling ES cell differentiation may be found in the early embryo because mouse ES cells form derivatives of all three embryonic germ layers upon injection into blastocysts. One promising candidate for influencing the differentiation of ES cells into the embryonic germ layers is the transforming growth factor-beta (TGF-beta) growth factor, Nodal. Nodal null mouse mutants lack mesoderm, and injection of Nodal mRNA into nonmammalian embryos induces mesodermal and endodermal tissues. We find that overexpression of Nodal in mouse ES cells leads not only to up-regulation of mesodermal and endodermal cell markers but also to downregulation of neuroectodermal markers. These findings demonstrate the importance of Nodal's influence on the differentiation of pluripotent cells to all three of the primary germ layers. Accordingly, altering expression of factors responsible for cell differentiation in the intact embryo provides an approach for directing ES cell fates in vitro toward therapeutically useful cell types.

Animals↗