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PubMed1999

Formation of a primitive ectoderm like cell population, EPL cells, from ES cells in response to biologically derived factors.

The primitive ectoderm of the mouse embryo arises from the inner cell mass between 4.75 and 5.25 days post coitum, around the time of implantation. Positioned at a pivotal time in development, just prior to formation of the three germ layers of the embryo proper, the primitive ectoderm responds directly to the signals generated during gastrulation. We have identified a conditioned medium, MEDII, which caused the homogeneous conversion of ES cells to a morphologically distinct cell population, termed early primitive ectoderm-like (EPL) cells. EPL cells expressed the pluripotent cell markers Oct4, SSEA1 and alkaline phosphatase. However, the formation of EPL cells was accompanied by alterations in Fgf5, Gbx2 and Rex1 expression, a loss in chimaera forming ability, changes in factor responsiveness and modified differentiation capabilities, all consistent with the identification of EPL cells as equivalent to the primitive ectoderm population of the 5.5 to 6.0 days post coitum embryo. EPL cell formation could be reversed in the presence of LIF and withdrawal of MEDII, which suggested that EPL cell formation was not a terminal differentiation event but reflected the ability of pluripotent cells to adopt distinct cell states in response to specific factors. Partial purification of MEDII revealed the presence of two separable biological activities, both of which were required for the induction and maintenance of EPL cells. We show here the first demonstration of uniform differentiation of ES cells in response to biological factors. The formation of primitive ectoderm, both in vivo and in vitro, appears to be an obligatory step in the differentiation of the inner cell mass or ES cells into cell lineages of the embryonic germ layers. EPL cells potentially represent a model for the development of lineage specific differentiation protocols and analysis of gastrulation at a molecular level. An understanding of the active components of MEDII may provide a route for the identification of factors which induce primitive ectoderm formation in vivo.

Animals↗
PubMed1975

The function of the ectodermal apical ridge and distinctive characteristics of adjacent distal mesoderm in the avian wing-bud.

Blocks of mesoderm about 0-1 mm in diameter were isolated from various regions of chick wing-buds of stages 17 through 22 and cultured individually, or sometimes in pairs, in microtest plate wells. Cell deaths had occurred after 10 h of culture in those explants that had come from the region associated with the thickest part of the ectodermal ridge, and after 11-12 h in all other mesoderm. When the adjacent ectodermal ridge was left attached to the mesodermal block there were almost no cell deaths for up to 24 h of culture. When the dorsal ectoderm immediately proximal to the apical ridge was left attached, but no ridge was present, cell deaths occurred just as they did in mesoderm with no ectoderm. When a number (usually six) of complete ridges were suspended in a wire basket at the top of a well, cell deaths did not occur in a test mesodermal block at the bottom of the well (six of eight cases). These experiments support previous evivence for a special function of the ectodermal apical ridge in limb morphogenesis, and indicate that there is a chemical messenger. The cells that migrated from distal mesodermal explants (the band up to 0-15 mm from the apical ridge) differed sharply in morphology and behavior from those coming from explants from any more proximal region. Within the proximal mesoderm there was a less striking variation alons the antero-posterior axis. These observations reveal that there is present even at early stages a detailed pattern within the mesoderm of the limb-bud. The particularly striking and distinctive characteristics of that mesoderm closest to the apical ectodermal ridge provide new possibilities for the understanding of the function of the ridge in limb morphogenesis.

Animals↗
PubMed1985

The origin of the ectodermal ring in staged human embryos of the first 5 weeks.

Seven embryos of stages 10-16 (3-5 weeks) were studied for their external form by means of graphic reconstructions. This is the first systematic report on the general surface anatomy of the early human embryo. The brain has been described and illustrated in a previous publication, and the present article is concerned particularly with an important although neglected feature: the ectodermal ring, described by Schmitt [Morph. Arb., Jena 8: 236-303, 1898] and named by Blechschmidt [Funktionsentwicklung. I. Mechanische Gegenwirkungen. Musterschmidt, Göttingen 1948]. Late in stage 10, three longitudinal bands can be seen on the surface: somitic, intermediate, and lateral plate. The intermediate band, which partly overlies nephrogenic tissue, is the site of the future ectodermal ring, which begins as an inverted U at stage 11 and is completed caudally in stage 12. The ectodermal ring, which may well be an important example of epithelial-mesenchymal interaction, comprises six parts: (a) rostral part, containing the situs neuroporicus, and olfactory and lens discs; (b) pharyngeal part, the covering of the pharyngeal arches; (c) occipital and cervicothoracic parts, related at first to the four occipital somites and later to the cervicothoracic junction; (d) membral part, represented by a preliminary ectodermal thickening, followed within 2 days by the apical ectodermal ridge; (e) intermembral part, related at first to the underlying coelom, and mesonephric duct and ridge; (f) caudal part, containing the cloacal membrane and a temporary 'caudal ectodermal ridge'. It is stressed that the incorrectly named 'Milchstreifen' is merely the intermembral part, in which the mammary crest ('Milchlinie' or 'Milchleiste') appears 1 week later.

Ectoderm↗
PubMed1982

An autoradiographic analysis of tissue potency in different regions of the embryonic ectoderm during gastrulation in the mouse.

In vitro chimaeras have been produced by injecting [3H]thymidine-labelled 8th day embryonic ectoderm, derived from the anterior, distal or posterior regions of the egg cylinder, into unlabelled synchronous embryos. Injected embryos were cultured for 36 h and the distribution of donor cells was analysed autoradiographically. One series of orthotopic injections was carried out and the results indicate that the developmental fate of embryonic ectoderm in the posterior part of the embryo is to form mesoderm, both embryonic and extraembryonic. Heterotopic injections of distal and posterior embryonic ectoderm demonstrate that these tissues readily conform to the colonisation patterns characteristic of their new location. In contrast, anterior embryonic ectoderm showed some preference for definitive ectoderm differentiation following heterotopic transplantation. However, there was no evidence that the normal fate of tissue from the three regions studied could be explained by pre-existing mosaicism in the embryonic ectoderm.

Animals↗
PubMed1982

Evidence that ectoderm influences the differentiation of muscle in the limb of the embryonic chick.

Intact limb buds from stage 19 to 21 embryos differentiate to contain both cartilage and muscle in culture. If the limb ectoderm is removed, the limb mesoderm cells differentiate as cartilage and connective tissue but not as muscle. Intact limb buds from stage 19 embryos differentiate both cartilage and muscle when grafted to the chorioallantoic membrane, but differentiate only cartilage and connective tissue if the ectoderm is removed. The significance of limb ectoderm to muscle differentiation can be observed as late as stage 24. Both the prospective cartilage region and the prospective soft tissue region from the limb of a stage 24 embryo differentiate cartilage and muscle in the presence of limb ectoderm, but differentiate little, if any, muscle in the absence of limb ectoderm. The results indicate that the dorsal and ventral ectoderm have some influence on muscle differentiation.

Animals↗
PubMed1996

Nuclear transplantation of ectodermal cells in pig oocytes: ultrastructure and radiography.

This study investigated the changes in nucleolar fine structure and the synthesis of both heterogeneous nuclear RNA (hnRNA) and ribosomal RNA (rRNA) in pig reconstructed embryos obtained by electrofusion of a single pig ectodermal cell to an enucleated metaphase-II oocyte. The nucleolar morphological changes and the pattern of transcription were examined in the ectodermal cells before fusion and in the nuclear transfer reconstructed embryos 16-18 hr after fusion. Before fusion the ectodermal cells exhibited a reticulated nucleolus with active RNA synthesis. In the reconstructed embryos, modifications of the nucleolar structure were observed, as assessed by the presence of either round-shaped, compact, dense nucleolar precursor bodies, or reticulated nucleoli. However, in both cases there was no RNA synthesis. Blebbing activity of the nuclear envelope was not observed. These results indicate that the nucleus of pig ectodermal cells exhibited either a complete or an incomplete remodelling when transferred to an enucleated metaphase-II oocyte, with no detectable RNA synthesis. Cell-cycle synchronization of ectodermal cell donor nuclei may play an important role in nuclear reprogramming after fusion.

Animals↗
PubMed1995

Glycoconjugate expression in the chick embryonic chorioallantoic membrane: comparisons of the chorionic ectoderm and allantoic endoderm.

BACKGROUND: The chorioallantoic membrane (CAM) of the chick embryo expands during embryogenesis to meet the increased oxygen demands during growth and differentiation. Temporal and spatial glycosylation patterns of CAM ectodermal and endodermal proteins likely contribute to differentiation of the functional attributes of the CAM. METHODS: Using lectins for light and electron microscopic observations, we studied the patterns of glycoconjugate expression on the ectoderm and endoderm of the chorioallantoic membrane (CAM) of the chick at days 4.5, 5.0, 5.5, 6.0, and 10 of morphogenesis. For light microscopy, samples of unfixed CAM were incubated with the following FITC lectins: Con A, DBA, GSA-I, GSA-II, PNA, SBA, UEA-I, and WGA. RESULTS: All lectins, except GSA-I and -II, gave positive results. The positive lectins, labeled with HRP, served to ultrastructurally localize PNA, SBA, and WGA, but not DBA binding to the luminal surface of the endoderm. UEA-I and Con A bound similarly except on day 10 when UEA-I no longer bound. On the ectodermal surface, only WGA bound at all times studied. PNA and SBA binding were present from days 5.0 to 6.0 but absent at days 4.5 and 10. DBA binding occurred through day 5.0 but was absent thereafter. UEA-I bound to the ectoderm at days 4.5, 5.0, and 10 but not days 5.5 and 6.0. Con A bound only on days 5.0 and 10. CONCLUSION: That the ultrastructurally similar ectoderm and endoderm of the CAM display functional differences conforms to the hypothesis that differential expression of glycoconjugate microdomains likely contributes to such functional specialization.

Allantois↗
PubMed1977

Effects of cytosine arabinoside, 6-aminonicotinamide, and 6-mercaptopurine riboside on ectoderm and mesoderm of mouse limb buds.

The effects of cytosine arabinoside, 6-aminonicotinamide, and 6-mercaptopurine riboside on the incorporation of [14C] glucose moieties and [32P] phosphate into acid-soluble material and lipids, RNA, DNA, and protein were measured in the dissected mesoderm and ectoderm of mouse limb buds at the 42-45 (day 11) somite stage. Due to the different proliferative capacities of the two tissues the incorporation of the precursors into mesodermal cells was considerably higher the than into ectodermal ones. Cytosine arabinoside inhibited the incorporation of the precursor moieties only into DNA, but very early after its application. This effect was more obvious in mesoderm than ectoderm. 6-Aminonicotinamide interfered only with glucose metabolism, whereas the incorporation of phosphate was not affected. 14C radioactivity in the various cell components was similarly reduced in mesoderm and ectoderm. 6-mercaptopurine riboside caused an increased incorporation of precursor material in all fractions studied in the mesoderm as well as in the ectoderm during the first 12 hours. This was succeeded by a dramatic decrease of incorporated 14C and 32P radioactivity. Differences of response in the tissues could not be detected with this drug. It is suggested that the malformations of the extrmities caused by these antimetabolites may be predominantly attributed to changes in the cell function rather than to gross effects on cell metabolism.

6-Aminonicotinamide↗
PubMed1992

A quantitative and morphological study of ectodermal microvilli in ten areas in the control and experimental prenatal rat.

This study provides a baseline of mainly quantitative morphologic information in relation to the ectodermal microvilli in ten areas in the control and experimental prenatal rat with special reference to the period of neural tube closure. Embryos from six litters were used and ten areas were examined mainly with the scanning electron microscope. Statistical analysis showed no significant difference between litters nor between the ten areas examined. In the 376 hr (day 15.6) fetus only the ectodermal cells of the nostril region demonstrated a rich population of microvilli, a fact possibly associated with late maturation of that region. Some evidence is provided to show that there is an increase in the population of microvilli in the 276 hr (day 11.5) embryo following experimentally induced zinc deficiency and introduction of nicotine in the culture medium. The possible mechanisms underlying the increase in ectodermal microvilli are i) an attempt by ectodermal cells to absorb nutrients, ii) a reflection of cells under stress, iii) failure of early embryonic ectodermal cells to shed microvilli normally associated with developmental changes, and iv) a generalized developmental delay rather than some cellular response to a trace element nutritional deficiency and a teratogen.

Animals↗
PubMed1994

An inhibitory effect of Xenopus gastrula ectoderm on muscle cell differentiation and its role for dorsoventral patterning of mesoderm.

In Amphibia, mesoderm cells such as notochord, muscle, and blood are formed as a result of mesoderm induction, the first known inductive interaction during the embryonic development of Vertebrates. Recent evidence shows, however, that, in addition to mesoderm induction, further cell-cell interactions during gastrulation also play an important role in the differentiation of mesoderm cells in Xenopus embryos. Here we report the existence of an inhibitory effect of gastrula ectoderm on muscle cell differentiation. When placed in contact with a muscle progenitor cell population, ectoderm from the ventral side of a gastrula embryo exerts an inhibitory effect on MyoD expression and muscle differentiation. This inhibitory effect is not observed on notochord differentiation. Dorsal ectoderm shows the same extent of inhibitory effect if it is isolated at the early-gastrula stage but gradually loses its effect during gastrulation as it is induced to become neural tissue. Cell mixing experiments have shown that this inhibitory effect, clearly seen in ventral ectoderm, is not observed in ventral mesoderm cells. We propose that the ectoderm emits a signal counteracting dorsalization and the community effect and that this signal plays an important role in the correct dorsoventral patterning of mesoderm.

Animals↗
PubMed1995

Identification of a spatially specific enhancer element in the chicken Msx-2 gene that regulates its expression in the apical ectodermal ridge of the developing limb buds of transgenic mice.

Msx-2 is a member of the Msx family of homeobox-containing genes expressed in a variety of embryonic tissues involved in epithelial-mesenchymal interactions and pattern formation. In the developing chick limb bud, Msx-2 is expressed in the apical ectodermal ridge, which plays a crucial role in directing the growth and patterning of limb mesoderm. In addition, Msx-2 is expressed in the anterior nonskeletal-forming mesoderm of the limb bud, in the posterior necrotic zone, and in the interdigital mesenchyme. Studies of the altered expression patterns of Msx-2 in amelic and polydactylous mutant chick limbs have suggested that the apical ectodermal ridge and mesodermal domains of Msx-2 expression are independently regulated and that there might be separate cis-regulatory elements in the Msx-2 gene controlling its spatially distinct domains of expression. To test this hypothesis, we have isolated the chicken Msx-2 gene and have tested the ability of various regions of the gene to target expression of LacZ reporter gene to specific regions of the limbs of transgenic mice. A variety of these constructs are consistently expressed only in the apical ectodermal ridge and the ectoderm of the genital tubercle and are not expressed in the mesoderm of the limb bud or in other regions of the embryo where the endogenous Msx-2 gene is expressed. These results suggest the presence of spatially specific cis-regulatory elements in the Msx-2 gene. We identified a 348-bp region in the 5' flanking region of the Msx-2 gene which can act as an apical ectodermal ridge enhancer element when placed in reverse orientation in front of the reporter gene with transcription initiation directed by the minimal hsp68 promoter.

Animals↗
PubMed1996

Overexpression of Xgsk-3 disrupts anterior ectodermal patterning in Xenopus.

The Xenopus homolog of glycogen synthase kinase-3, Xgsk-3, plays a major role in regulating the formation of the dorsal-ventral axis, most likely through effects on the mesoderm. To determine whether Xgsk-3 is involved in ectodermal patterning, Xgsk-3 was ectopically overexpressed in the presumptive ectoderm. This approach resulted in a dramatically expanded cement gland, which is due to early changes in cement gland specification at the anterior end of the embryo. Explant experiments were used to show that Xgsk-3 overexpression enhances the response of ectoderm to cement-gland-inducing signals from the mesoderm and to the intercellular signaling factor noggin. Expression of two other noggin-inducible genes, Xotx2 and XANF-2, was also expanded in whole embryos, while the expression of the epidermal marker, Xgbx-2, was eliminated. These results suggest that Xgsk-3 may play a role in anterior ectodermal patterning as a component of an intracellular pathway that regulates the ectodermal responsiveness to endogenous inducing signals.

Animals↗
PubMed1997

Regulation of paraxis expression and somite formation by ectoderm- and neural tube-derived signals.

During vertebrate embryogenesis, the paraxial mesoderm becomes segmented into somites, which form as paired epithelial spheres with a periodicity that reflects the segmental organization of the embryo. As a somite matures, the ventral region gives rise to a mesenchymal cell population, the sclerotome, that forms the axial skeleton. The dorsal region of the somite remains epithelial and is called dermomyotome. The dermomyotome gives rise to the trunk and limb muscle and to the dermis of the back. Epaxial and hypaxial muscle precursors can be attributed to distinct somitic compartments which are laid down prior to overt somite differentiation. Inductive signals from the neural tube, notochord, and overlying ectoderm have been shown to be required for patterning of the somites into these different compartments. Paraxis is a basic helix-loop-helix transcription factor expressed in the unsegmented paraxial mesoderm and throughout epithelial somites before becoming restricted to epithelial cells of the dermomyotome. To determine whether paraxis might be a target for inductive signals that influence somite patterning, we examined the influence of axial structures and surface ectoderm on paraxis expression by performing microsurgical operations on chick embryos. These studies revealed two distinct phases of paraxis expression, an early phase in the paraxial mesoderm that is dependent on signals from the ectoderm and independent of the neural tube, and a later phase that is supported by redundant signals from the ectoderm and neural tube. Under experimental conditions in which paraxis failed to be expressed, cells from the paraxial mesoderm failed to epithelialize and somites were not formed. We also performed an RT-PCR analysis of combined tissue explants in vitro and confirmed that surface ectoderm is sufficient to induce paraxis expression in segmental plate mesoderm. These results demonstrate that somite formation requires signals from adjacent cell types and that the paraxis gene is a target for the signal transduction pathways that regulate somitogenesis.

Amino Acid Sequence↗
PubMed1997

The homeobox gene PV.1 mediates specification of the prospective neural ectoderm in Xenopus embryos.

Bone morphogenetic protein 4 (BMP4), a member of the TGF beta superfamily, has been implicated in the dorsoventral specification of both mesoderm and ectoderm. High levels of BMP4 signaling appear to specify ventral lineages, while lower levels are causally associated with the development of dorsal lineages. We have previously identified a homeobox-containing transcription factor (PV. 1) which is a likely mediator of the ventralizing effects of BMP4 in the mesoderm. Here we provide evidence that PV.1 also functions downstream of BMP4 in the patterning of ectoderm, specifying epidermal and suppressing neural gene expression. PV.1 is expressed in the prospective neuroectoderm at the time of ectodermal fate determination. BMP4 and xSmad1 (a downstream effector of BMP4) induce PV.1 in uncommitted ectoderm and the dominant negative form of the BMP4 receptor (DN-BR) blocks PV.1 expression. In animal pole explants PV.1 counteracts the neuralizing effects of chordin and the DN-BR and restores them to their original epidermal fate. To address the physiological significance of these observations we employed an animal cap transplantation system and demonstrated that overexpression of PV.1 in the prospective neuroectoderm specifically blocks neurogenesis in intact embryos. Thus, PV.1 plays an important role in the ventralization of both mesoderm and ectoderm. We have previously shown that PV.1 is also preferentially expressed in the ventral endoderm, suggesting that this transcription factor may be involved in the ventralization of all three germ layers.

Amino Acid Sequence↗
PubMed1994

[Pili torti et canaliculi in ectodermal dysplasia].

Uncombable hair is a heterogeneous symptom with a partially genetic background. In order to make an exact diagnosis, it is mandatory to recognize associated abnormalities, do pedigree analyses, and perform scanning electron microscopic studies of the hair. In a case of ectodermal dysplasia, ectrodactyly, cleft lip/palate (EEC) syndrome and in a patient with familial tricho-odonto-onychial ectodermal dysplasia with syndactyly, scanning electron microscopy demonstrated pili torti et canaliculi, helicotrichia and cuticular dystrophy. Congenital pili torti et canaliculi must be differentiated from pili torti and from pili trianguli et canaliculi ("cheveux incoiffables"), inasmuch as they may present in hypotrichosis congenita hereditaria of Marie-Unna or as part of complex ectodermal dysplasia syndromes with clefting of the lip/palate and/or limb defects. It is noteworthy that some of those patients show a dysmorphic facies and an atopic constitution in addition to the aforementioned abnormalities. We discuss the possible relationship of these syndromes to each other, with special respect to the Hay-Wells or ankyloblepharon, ectodermal dysplasia, cleft lip/palate (AEC) and the Rapp-Hodgkin (ectodermal dysplasia, midfacial hypoplasia, cleft lip/palate) syndromes.

Abnormalities, Multiple↗
PubMed1987

The ectodermal control of mesodermal patterns of differentiation in the developing chick wing.

The influence of limb ectoderm on the dorso-ventral muscle and skeletal patterns in the chick wing was studied by recombining stage 14-21 limb mesoderm with the same stage ectoderm in dorso-ventrally reversed orientation. Recombinants grafted to the flank of host embryos were allowed to develop for 10 days. Fully developed wings obtained from stage 15-21 donor embryos have at their distal half d-v polarity conforming to the reversed ectoderm and proximally polarity conforming with the mesoderm. The ectodermal effect is generally observed as a bidorsal feather pattern at the autopod and an almost complete d-v reversal of muscle and skeletal patterns. In experimental wings from donor embryos younger than stage 15, the dorso-ventral pattern conforms with the polarity of the limb mesoderm. The results suggest that control of dorso-ventral polarity resides in the mesoderm until the onset of limb development at stage 15. At this stage, the ectoderm acquires dorso-ventral information which it can impose on the mesoderm.

Animals↗
PubMed1989

Experimental analysis of the in vivo chondrogenic potential of the interdigital mesenchyme of the chick leg bud subjected to local ectodermal removal.

Current in vitro investigations suggest that ectoderm plays a major role in limb morphogenesis by producing a diffusible factor which inhibits the chondrogenesis of the underlying mesenchyme. In the present work we report evidence supporting such an ectodermal role in vivo. Surgical removal of the marginal ectoderm from the third interdigit of chick leg buds at stages 27 to 30 induces the formation of PNA-positive prechondrogenic mesenchymal condensations 15 hr after the operation. The incidence of prechondrogenic condensations achieved 47, 95.2, and 92.8 of the experimental embryos of stages 27, 28, and 29, respectively. This high rate of prechondrogenic aggregate formation contrasted with a lower incidence of ectopic cartilage formation detectable by Alcian blue staining 40 hr after the operation. The sequential analysis of the experimental interdigits by means of peanut lectin labeling suggests that a number of prechondrogenic condensations undergo disaggregation 20 and 30 hr after the operation failing to form fully differentiated cartilages. When ectoderm removal was accompanied by the elimination of a variable amount of interdigital mesenchyme the incidence of prechondrogenic aggregates showed little differences but the formation of fully differentiated cartilages was reduced at a rate proportional to the amount of interdigital mesenchyme removed. From this study it can be concluded that the ectoderm in vivo appears to inhibit the process of aggregation of the mesenchymal cells to form prechondrogenic condensations. Furthermore our results suggest that as observed in vitro (C. P. Cotrill, C. Archer, and L. Wolpert, 1987, Dev. Biol. 122, 503-515) the transformation of prechondrogenic aggregates into fully differentiated cartilage requires the involvement of a critical amount of mesenchymal cells.

Alcian Blue↗
PubMed1990

Extracellular matrix components prevent neural differentiation of disaggregated Xenopus ectoderm cells.

Neuralization (archencephalic brain formation) takes place after dissociation and delayed reaggregation of animal caps of early gastrula without inducer (Grunz, H. and L. Tacke: Cell Differ. Dev. 28, 211-218 (1989)). This autoneuralization can be prevented by the cell supernatant from dissociated ectoderm of Xenopus laevis, which contains extracellular matrix components. After phenol extraction of the supernatant, the aqueous phase does no longer show inhibitory activity. It can be concluded from these results that glycoconjugates responsible for the prevention of neuralization represent glycoproteins or proteoglycans which are loosely attached to integral plasma membrane components. Single early gastrula ectoderm cells mixed with non-competent late gastrula ectoderm or endoderm, which primarily form common aggregates, do not differentiate into neural derivatives. In these reaggregates the ectoderm cells remain separated from each other by heterologous cells (non-competent ectoderm or endodermal cells) during the period of competence. These data indicate that the quick recovery of extracellular matrix components together with the restoration of the former organization of the plasma membrane is responsible for the prevention of neuralization.

Animals↗