Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Embryonic Induction”

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 1,585 records · Page 88Linked to original sources
PubMed1994

Drosophila wingless: a paradigm for the function and mechanism of Wnt signaling.

The link between oncogenesis and normal development is well illustrated by the study of the Wnt family of proteins. The first Wnt gene (int-1) was identified over a decade ago as a proto-oncogene, activated in response to proviral insertion of a mouse mammary tumor virus. Subsequently, the discovery that Drosophila wingless, a developmentally important gene, is homologous to int-1 supported the notion that int-1 may have a role in normal development. In the last few years it has been recognized that int-1 and Wingless belong to a large family of related glyco-proteins found in vertebrates and invertebrates. In recognition of this, members of this family have been renamed Wnts, an amalgam of int and Wingless. Investigation of Wnt genes in Xenopus and mouse indicates that Wnts have a role in cell proliferation, differentiation and body axis formation. Further analysis in Drosophila has revealed that Wingless function is required in several developmental processes in the embryo and imaginal discs. In addition, a genetic approach has identified some of the molecules required for the transmission and reception of the Wingless signal. We will review recent data which have contributed to our growing understanding of the function and mechanism of Drosophila Wingless signaling in cell fate determination, growth and specification of pattern.

Animals↗
PubMed1997

Fish are like flies are like frogs: conservation of dorsal-ventral patterning mechanisms.

Genetic analysis of Drosophila has shown that a morphogenetic gradient of the Transforming Growth Factor-beta family member dpp patterns the embryonic dorsal-ventral axis. Molecular and embryological evidence from Xenopus has strongly suggested a similar role for Bmp-4, the dpp homolog, in patterning the dorsal-ventral axis of chordates. A recent report has now identified mutations in two genes, dino and swirl, that disrupt dorsal-ventral patterning in the zebrafish Danio rerio. Characterization of these mutations parallels findings from Drosophila, thus establishing a genetic framework for the analysis of dorsal-ventral patterning in a vertebrate.

Animals↗
PubMed1997

Morphogens and pattern formation.

Morphogen gradient theories have enjoyed considerable popularity since the beginning of this century, but conclusive evidence for a role of morphogens in controlling multicellular development have been elusive. Recently, work on three secreted signalling proteins. Activin in Xenopus, and Wingless and Dpp in Drosophila, has strongly suggested that these proteins function as morphogens. In order to define a factor as a morphogen, it is necessary to show firstly, that it has a direct effect on target cells and secondly, that it affects the development of target cells in a concentration-dependent manner. With these criteria in mind, the evidence available for a variety of proposed morphogens is discussed. While the evidence is not conclusive in most of the cases considered, there is a strong case in favour of the three proteins mentioned above, which suggests that morphogens are potentially of general importance in controlling the development of multicellular organisms.

Activins↗
PubMed2002

Efficiency of embryoid body formation and hematopoietic development from embryonic stem cells in different culture systems.

Embryonic stem (ES) cells have tremendous potential as a cell source for cell-based therapies. Realization of that potential will depend on our ability to understand and manipulate the factors that influence cell fate decisions and to develop scalable methods of cell production. We compared four standard ES cell differentiation culture systems by measuring aspects of embryoid body (EB) formation efficiency and cell proliferation, and by tracking development of a specific differentiated tissue type-blood-using functional (colony-forming cell) and phenotypic (Flk-1 and CD34 expression) assays. We report that individual murine ES cells form EBs with an efficiency of 42 +/- 9%, but this value is rarely obtained because of EB aggregation-a process whereby two or more individual ES cells or EBs fuse to form a single, larger cell aggregate. Regardless of whether EBs were generated from a single ES cell in methylcellulose or liquid suspension culture, or aggregates of ES cells in hanging drop culture, they grew to a similar maximum cell number of 28,000 +/- 9,000 cells per EB. Among the three methods for EB generation in suspension culture there were no differences in the kinetics or frequency of hematopoietic development. Thus, initiating EBs with a single ES cell and preventing EB aggregation should allow for maximum yield of differentiated cells in the EB system. EB differentiation cultures were also compared to attached differentiation culture using the same outputs. Attached colonies were not similarly limited in cell number; however, hematopoietic development in attached culture was impaired. The percentage of early Flk-1 and CD34 expressing cells was dramatically lower than in EBs cultured in suspension, whereas hematopoietic colony formation was almost completely inhibited. These results provide a foundation for development of efficient, scalable bioprocesses for ES cell differentiation, and inform novel methods for the production of hematopoietic tissues.

Animals↗
PubMed2004

Bioreactor cultivation enhances the efficiency of human embryoid body (hEB) formation and differentiation.

The promise of human embryonic stem cells (hESCs) to provide an unlimited supply of cells for cell therapy and tissue engineering depends on the availability of a controllable bioprocess for their expansion and differentiation. We describe for the first time the formation of differentiating human embryoid bodies (hEBs) in rotating bioreactors to try and control their agglomeration. The efficacy of the dynamic process compared to static cultivation in Petri dishes was analyzed with respect to the yield of hEB formation and differentiation. Quantitative analyses of hEBs, DNA and protein contents, and viable cell concentration, as measures for culture cellularity and scale-up, revealed 3-fold enhancement in generation of hEBs compared to the static culture. Other metabolic indices such as glucose consumption, lactic acid production, and pH pointed to efficient cell expansion and differentiation in the dynamic cultures. The type of rotating vessel had a significant impact on the process of hEB formation and agglomeration. In the slow turning lateral vessel (STLV), hEBs were smaller in size and no large necrotic centers were seen, even after 1-month cultivation. In the high aspect rotating vessel (HARV), hEB agglomeration was massive. The appearance of representative tissues derived from the three germ layers as well as primitive neuronal tube organization, blood vessel formation, and specific-endocrine secretion indicated that the initial developmental events are not altered in the dynamically formed hEBs. Collectively, our study defines the culture conditions in which control over the aggregation of differentiating hESCs is obtained, thus enabling scaleable cell production for clinical and industrial applications.

Apoptosis↗
PubMed2003

Paleocortex is specified in mice in which dorsal telencephalic patterning is severely disrupted.

The patterning of the telencephalon is regulated by the concerted action of distinct mechanisms operating in different portions of this structure. Although much progress has been made in understanding the mechanisms underlying the specification of dorsal and ventral structures, little is known about the specification of the paleocortex, the olfactory cortex located at the interface of the dorsal and ventral telencephalon. The paleocortex is thought to be a dorsal, cortical structure, derived from the lateral extreme of the dorsal telencephalon. We examined mutant mice in which dorsal telencephalic patterning is severely disrupted, to ask how these perturbations affect the paleocortex. In the Lhx2-/- telencephalon, where the cortex is greatly shrunken such that medial and dorsal cortical tissue is undetectable, normal expression of several paleocortical markers is observed. The Gli3-/- telencephalon, where the dorsal telencephalon is ventralized, also displays paleocortical markers. In contrast, when the ventral telencephalon is almost completely deleted, such as in the BF1-/- brain, paleocortical markers are undetectable. These results indicate that the specification of the paleocortex can occur in spite of drastic perturbations of dorsal patterning. Furthermore, in the Lhx2 mutant, the paleocortex is juxtaposed to an expanded and mislocated source of Wnt and Bmp signaling, the cortical hem, whereas, in the Gli3 mutant, paleocortical markers arise even though the cortical hem is missing. This indicates that an increase or decrease in cues from this dorsal signaling center does not disrupt the specification of the paleocortex. Finally, by using an in vitro assay, we found that isolated explants of lateral telencephalon up-regulate normal expression of paleocortical markers when maintained in vitro, from as early as embryonic day (E) 10.5. Together, the results reveal that, although the paleocortex is considered to be a cortical structure, it is specified even when dorsal telencephalic patterning is grossly perturbed. Furthermore, our in vitro data reveal that, if mechanisms outside the lateral telencephalon are involved in the specification of the paleocortex, they must act extremely early, prior to E10.5.

Animals↗
PubMed2005

Dlx gene expression during chick inner ear development.

Members of the Dlx gene family play essential roles in the development of the zebrafish and mouse inner ear, but little is known regarding Dlx genes and avian inner ear development. We have examined the inner ear expression patterns of Dlx1, Dlx2, Dlx3, Dlx5, and Dlx6 during the first 7 days of chicken embryonic development. Dlx1 and Dlx2 expression was seen only in nonneuronal cells of the cochleovestibular ganglion and nerves from stage 21 to stage 32. Dlx3 marks the otic placode beginning at stage 9 and becomes limited to epithelium adjacent to the hindbrain as invagination of the placode begins. Dlx3 expression then resolves to the dorsal otocyst and gradually becomes limited to the endolymphatic sac by stage 30. Dlx5 and Dlx6 expression in the developing inner ear is first seen at stages 12 and 13, respectively, in the rim of the otic pit, before spreading throughout the dorsal otocyst. As morphogenesis proceeds, Dlx5 and Dlx6 expression is seen throughout the forming semicircular canals and endolymphatic structures. During later stages, both genes are seen to mark the distal surface of the forming canals and display expression complementary to that of BMP4 in the vestibular sensory regions. Dlx5 expression is also seen in the lagena macula and the cochlear and vestibular nerves by stage 30. These findings suggest important roles for Dlx genes in the vestibular and neural development of the avian inner ear.

Amino Acid Sequence↗
PubMed2005

BOC, brother of CDO, is a dorsoventral axon-guidance molecule in the embryonic vertebrate brain.

The early axon scaffolding in the embryonic vertebrate brain consists of a series of ventrally projecting axon tracts that grow into a single major longitudinal pathway connected across the midline by commissures. We have investigated the role of Brother of CDO (BOC), an immunoglobulin (Ig) superfamily member distantly related to the Roundabout (Robo) family of axon-guidance receptors, in the development of this embryonic template of axon tracts in the zebrafish brain. A zebrafish homologue of BOC was isolated and shown to be expressed predominantly in the developing neural plate and later in the neural tube and developing brain. Zebrafish boc was initially highly localized to discrete bands in the mid- and hindbrain, but, as the major brain subdivisions emerged, it became more evenly expressed along the rostrocaudal axis, particularly in dorsal regions. The function of zebrafish boc was examined by a loss-of-function approach. Analysis of embryos injected with antisense morpholinos designed against boc revealed highly selective defects in the development of dorsoventrally projecting axon tracts. Loss of boc caused ventrally projecting axons, particularly those arising from the presumptive telencephalon, to follow aberrant trajectories. These data indicate that boc is an axon-guidance molecule playing a fundamental role in pathfinding during the early patterning of the axon scaffold in the embryonic vertebrate brain.

Animals↗
PubMed1979

Substrate pathways which guide growing axons in Xenopus embryos.

Optic axons from eyes transplanted to hindbrain and spinal cord (i.e., non-optic areas) in Xenopus embryos reproducibly follow a particular pair of continuous tracts, the external sensory tract and the internal sensory tract. The course of the external sensory tract may coincide with the course of the general somatic afferent tracts (i.e., the ascending and descending tracts of nerve V, the tract of Lissauer, and the Rohon-Beard cell tracts). The course of the internal sensory tract parallels that of the external sensory tract but runs more medially. Transplanted optic axons follow the same tracts regardless of where along the neural axis the axons have entered the CNS. What kind of developmental cues guide these optic axons? It is unlikely that the guidance cues are organized as spatial coordinates, rather it appears that the optic axons of these two tracts are guided along pre-existing substrate routes. We have called these routes substrate pathways. Substrate pathways may be a device normally used for organizing fiber tracts in the developing nervous system.

Animals↗
PubMed1981

Substrate pathways demonstrated by transplanted Mauthner axons.

A substrate pathway is a set of aligned guidance cues. (Such cues may be either cells or molecules.) CNS substrate pathways can be demonstrated by transplanting axons to different starting locations. The stereotyped routes of transplanted axons will then demonstrate the locations of effective substrate pathways. To map CNS substrate pathways, Mauthner axons were transplanted to various unnatural locations along the CNS of Xenopus embryos. The routes of 24 experimental Mauthner axons were traced. Twenty-one of these axons grew along parts of a stereotyped route extending in the ventral marginal zone from the caudal diencephalon through the spinal cord. This ventral substrate pathway ran the length of the basal plate; thus, we call it a basal substrate pathway. One experimental Mauthner axon grew along the alar substrate pathway previously demonstrated by transplanted optic axons. The demonstrations of the alar and the basal substrate pathways suggest that during development a few long substrate pathways organize the overall layout of the long tracts of the CNS. We propose that the pattern of the earliest CNS substrate pathways is established in the neural plate and is topologically preserved as the neural plate rolls into a neural tube. This pattern may be manifest as the three-dimensional organization of the early marginal zones formed by the peripheral processes (the endfeet) of certain developing ependyma and radial glia. Subsequently, the detailed anatomy of the axon tracts and the specific terminations of individual axons are probably determined by other local chemical cues.

Brain↗
PubMed1983

Developmental relationships between trigeminal ganglia and trigeminal motoneurons in chick embryos. II. Ganglion axon ingrowth guides motoneuron migration.

In the chick embryo the trigeminal (V) sensory ganglion cells send axons into the metencephalon a few hours before the V motoneurons migrate from the midline to form a lateral nucleus adjacent to the ingrowing sensory axons. This relationship suggests that the ganglion axons may influence the initiation and direction of V motoneuron migration. In the present experiment the development of the ganglion axons was retarded by removing the neural crest anlage of the V ganglion. Subsequently, V ganglion cells which were derived from the ectodermal placode anlage sent axons into the metencephalon up to 2 days later than normal. The lateral migration of the V motoneurons was similarly delayed, commencing only after the central axons from the placodal ganglia penetrated the metencephalon. This study demonstrates that the presence of V ganglion perikarya alone is not sufficient to guide the appropriate migration of V motoneurons. This migration occurs only after the axons from the V sensory ganglion cells have penetrated the brainstem.

Animals↗
PubMed1983

Developmental relationships between trigeminal ganglia and trigeminal motoneurons in chick embryos. III. Ganglion perikarya direct motor axon growth in the periphery.

The previous study in this series demonstrated that the ingrowth of the central axons of the trigeminal (V) ganglion is prerequisite to V motor axon outgrowth and somatic translocation. In the present experiment we determined whether further interactions with V ganglion cell bodies were required by V motoneurons after the V ganglion innervates the brainstem. Soon after the ganglion axons had penetrated the brainstem they were severed, and a barrier, either permeable or impermeable, was placed between the ganglion cell bodies and the metencephalon. V motor axons grew along aberrant pathways to circumvent the impermeable barriers, many rerouting to reach the V ganglion. Only those V motor nerves which contacted the V ganglion distal to the barrier reached their target musculature in the mandible. The pattern of migration of V motoneurons was normal regardless of the V motor nerve trajectory, but the cell bodies of those axons which did not reach a muscle were not fully differentiated. When permeable barriers (Millipore filters) were implanted, the nerves followed two types of trajectories. If the pore size of the filter was small (0.45 and 0.025 microns), the V motor nerves grew identically to those observed in embryos in which impermeable barriers had been implanted. If the pore size of the filter was large (8.0 and 0.08 microns), the V motor nerve grew along its normal path directly to the barrier. Small axonal bundles from these nerves frequently grew into the filter toward the distal V ganglion. These results indicate that V motor axons preferentially grow to the V ganglion perikarya after exiting from the brainstem. Contact with the V ganglion always results in V motor nerve growth to the mandible while growth of the V motor axons to aberrant target sites only occurs when the axons fail to contact the V ganglion cells distal to the barrier.

Animals↗
PubMed1983

Development of fetal retina, tectum, and cortex transplanted to the superior colliculus of adult rats.

Earlier studies showed that embryonic retina, cortex, or tectum transplanted adjacent to the superior colliculus of newborn host rats differentiated many of the histological features appropriate for the donor region and developed interconnections with the host nervous system. In the study presented here, the same regions were transplanted to the brain of adult host rats and the development of these transplants was compared to those into newborn hosts. Retina, rostral tectum, or occipital cortex was dissected from donor rat embryos on gestational day 14 or 15. A portion of cortex was aspirated in 2-month-old host rats to expose the right superior colliculus, and one of the donor tissues was placed adjacent to the colliculus in each host. Two to 4 months after transplantation, transplant histology and neuronal interconnections between the transplant and host nervous system were studied by using Nissl and neurofibrillar stains and 3H-proline and HRP tract tracing techniques. Four main points can be drawn from these results. First, 80% of the transplants survived in adult hosts - a percentage comparable to that found in newborn hosts. Second, each of the types of tissues transplanted differentiated histological characteristics appropriate for its site or origin, although the degree of differentiation was always much less than in transplants to newborns. Third, the transplants developed only relatively local projections into the host cortex and superior colliculus. This contrasts with the extensive projections found from the transplants into the brain of newborn hosts. Fourth, no definitive projections from the host retina or brain were identified to any of the transplants into adults, whereas both cortical and tectal transplants into newborns received projections from the host.

Age Factors↗
PubMed1983

The organization of the fibers in the optic nerve of normal and tectum-less Rana pipiens.

We have examined the detailed order of retinal ganglion cell (RGC) axons in the optic nerve and tract of the frog, Rana pipiens. By using horseradish peroxidase (HRP) injections into small regions of the retina, the tectum, and at various points along the visual pathway, it has been possible to follow labelled fibers throughout their course in the nerve and tract. Several surprising features in the order of fibers in the visual pathway were discovered in our investigation. The fascicular pattern of RGC axons in the retina is similar to that described in other vertebrates; however, immediately central to their entry into the optic nerve head, approximately half of the fibers from the nasal or temporal retina cross over to the opposite side of the nerve. Although the axons from the dorsal and ventral regions of the retina generally remain in the dorsal and ventral regions of the nerve, some fiber crossing occurs in those axons as well. The result of this seemingly complex rearrangement is that the optic nerve of Rana pipiens contains mirror symmetric representations of the retinal surface on either side of the dorsal ventral midline of the nerve. The fibers in each of these representations are arranged as semicircles representing the full circumference of the retina. This precise fiber order is preserved in the nerve until immediately peripheral to the optic chiasm, at which point age-related axons from both sides of the nerve bundle together. Consequently, when a small pellet of HRP is placed in the chiasmic region of the nerve, an annulus of retinal ganglion cells and a corresponding annulus of RGC terminals in the tectum are labelled. As the age-related bundles of fibers emerge from the chiasm they split to form a medial bundle and a lateral bundle, which grow in the medial and lateral branches of the optic tract, respectively. Although the course followed by RGC axons in the visual pathway is complex, we propose a model in which the organization of fibers in the nerve and tract can arise from a few rules of axon guidance. To determine whether the optic tecta, the primary retinal targets, play a role in the development and organization of the optic nerve and tract, we removed the tectal primordia in Rana embryos and examined the order in the nerve when the animals had reached larval stages. We found that the order in the nerve and tract was well preserved in tectumless frogs. Therefore, we propose that guidance factors independent of the target direct axon growth in the frog visual system.

Animals↗
PubMed1987

Specific neurotrophic interactions between cortical and subcortical visual structures in developing rat: in vitro studies.

We investigated the influence of different subcortical structures on the survival of specific populations of occipital cortex neurons developing in vitro. Explants of embryonic day 14-15 (E14-15) rat cortex were cultured for 5 days with explants of either diencephalon or optic tectum or another occipital cortex explant. Stereological analysis of the explants revealed that after 5 days in vitro (5 DIV) all the cortical explants contained equal proportions of healthy neurons, glia, neuropil, and degenerating profiles, regardless of the culturing conditions. In order to determine if different neuronal populations survived preferentially in the cortical explants as a result of the presence of potential target or afferent structures, we used HRP filling and 3H-thymidine labeling techniques. Specific differences in the morphology of the cells and their time of origin are found in the cortical explants. In the cortical explants cocultured with diencephalon (Cx + D) the cortical cells that survive tend to be round with small cross-sectional areas and have few neurites. These cells are generated late in the culturing period. The surviving cortical neurons in the cortex plus tectum (Cx + T) cultures are larger--many with a pyramidal-shaped soma and several neurites. These cells are generated earlier in vitro. The cortex cultured with other cortex (Cx + Cx) gives values intermediate to the Cx + D and Cx + T cultures. The results of these experiments suggest that there are diffusible trophic factors that arise from subcortical structures that selectively support the survival of neuron populations in the developing neocortex.

Animals↗
PubMed2002

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates.

Gene-targeted disruption of Grg5, a mouse homologue of Drosophila groucho (gro), results in postnatal growth retardation in mice. The growth defect, most striking in approximately half of the Grg5 null mice, occurs during the first 4-5 weeks of age, but most mice recover retarded growth later. We used the nonlinear mixed-effects model to fit the growth data of wild-type, heterozygous, and Grg5 null mice. On the basis of preliminary evidence suggesting an interaction between Grg5 and the transcription factor Cbfa1/Runx2, critical for skeletal development, we further investigated the skeleton in the mice. A long bone growth plate defect was identified, which included shorter zones of proliferative and hypertrophic chondrocytes and decreased trabecular bone formation. This decreased trabecular bone formation is likely caused by a reduced recruitment of osteoblasts into the growth plate region of Grg5 null mice. Like the growth defect, the growth plate and trabecular bone abnormality improved as the mice grew older. The growth plate defect was associated with reduced Indian hedgehog expression and signaling. We suggest that Grg5, a transcriptional coregulator, modulates the activities of transcription factors, such as Cbfa1/Runx2 in vivo to affect Ihh expression and the function of long bone growth plates.

Animals↗
PubMed2003

Establishment of a ventral cell fate in the spinal cord.

The neural plate is induced during gastrulation when the organizer affects the ectoderm around it. Recent experiments show that axial mesoderm can stimulate formation of specific ventral cell types in the spinal cord, including floor plate, motor neurons, and several types of interneurons. We have eliminated or disrupted axial mesoderm by using a variety of methods to show that ventral columns of intermittent dopaminergic neurons in the frog Xenopus also appear to be induced by axial mesoderm. Inversion of the dorsal-ventral neural axis by splitting the presumptive neural plate in vivo, produced two spinal cords with ectopic dopaminergic neurons. The location and number of neurons suggest that even a brief association with axial mesoderm can specify the identity of the first or primary dopaminergic neurons and that notochord retains the ability to induce cells to become secondary dopaminergic neurons.

Animals↗
PubMed2001

Induction of bud formation of embryonic mouse tracheal epithelium by fibroblast growth factor plus transferrin in mesenchyme-free culture.

Embryonic mouse tracheal epithelium, which branches in an epithelial-mesenchymal recombination culture with bronchial mesenchyme, was cultured under mesenchyme-free conditions. When embedded in a basement-membrane-like matrix and cultured in a serum-free medium supplemented with fibroblast growth factor 1 (FGF1), the tracheal epithelium did not branch, whereas the bronchial epithelium underwent branching morphogenesis. When the medium was enriched with transferrin (Tf), bud formation was induced in the tracheal epithelium and some buds branched secondarily. FGF7 and FGF10, in cooperation with Tf, induced tracheal bud formation to the same extent as FGF1, although the optimum concentrations differed. A bromodeoxyuridine-labeling study comparing cultures with and without Tf showed no Tf-specific amplification of cell proliferation. A whole-mount in situ hybridization study of the expression of Bmp4 and Shh genes in explants of mesenchyme-free culture revealed that both genes were ubiquitously expressed and that expression did not correlate with bud formation. This expression pattern was different from the distally localized expression pattern observed in normal lung rudiments and in extratracheal buds induced by the recombined bronchial mesenchyme. These results suggest that both bronchial and tracheal bud formations were initiated without localized exposure of the epithelium to FGFs and were not accompanied by localized expression of Bmp4 and Shh in the epithelium.

Age Factors↗