SEARCH · PubMed Health

Results for “inner ectoderm”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 91 records · Page 5Linked to original sources

PubMed1985

Regeneration of endoderm from primitive ectoderm in the mouse embryo: fact or artifact?

The capacity of immunosurgically (IS) treated inner cell masses (ICMs) versus microsurgically (MS) isolated primitive ectoderms from blastocysts recovered on the 5th day of gestation to regenerate an external layer of endoderm cells in vitro was investigated. While the majority of IS-treated ICMs regenerated such a layer, MS-isolated ectoderms seldom did so. Examination of the two types of tissue fragments revealed that IS-treated ICMs almost invariably retained viable endoderm cells whereas MS-isolated ectoderms did so only exceptionally. The endoderm was found to be more than one cell layer thick in ICMs from 5th day blastocysts, suggesting that some endoderm cells survive IS because they are protected from exposure to antiserum. Typing of the endoderm layer that regenerated following IS treatment of recombinant ICMs composed of genetically dissimilar endoderm and ectoderm provided direct evidence that it originated from residual endoderm cells rather than the underlying ectoderm. Finally, blastocyst injection experiments confirmed that IS-treated ICMs behave like a mixture of ectoderm and endoderm tissue in vivo, and provided no support for the view that cells of the original and regenerated endoderm differ in developmental potential. These findings challenge earlier conclusions concerning cell lineage and determination in the primitive ectoderm that were based on development in vitro of IS-treated ICMs from giant blastocysts.

Animals↗

PubMed2006

Role of the hindbrain in patterning the otic vesicle: a study of the zebrafish vhnf1 mutant.

The vertebrate inner ear develops from an ectodermal placode adjacent to rhombomeres 4 to 6 of the segmented hindbrain. The placode then transforms into a vesicle and becomes regionalised along its anteroposterior, dorsoventral and mediolateral axes. To investigate the role of hindbrain signals in instructing otic vesicle regionalisation, we analysed ear development in zebrafish mutants for vhnf1, a gene expressed in the caudal hindbrain during otic induction and regionalisation. We show that, in vhnf1 homozygous embryos, the patterning of the otic vesicle is affected along both the anteroposterior and dorsoventral axes. First, anterior gene expression domains are either expanded along the whole anteroposterior axis of the vesicle or duplicated in the posterior region. Second, the dorsal domain is severely reduced, and cell groups normally located ventrally are shifted dorsally, sometimes forming a single dorsal patch along the whole AP extent of the otic vesicle. Third, and probably as a consequence, the size and organization of the sensory and neurogenic epithelia are disturbed. These results demonstrate that, in zebrafish, signals from the hindbrain control the patterning of the otic vesicle, not only along the anteroposterior axis, but also, as in amniotes, along the dorsoventral axis. They suggest that, despite the evolution of inner ear structure and function, some of the mechanisms underlying the regionalisation of the otic vesicle in fish and amniotes have been conserved.

Animals↗

PubMed2006

Retinoid signaling in inner ear development.

The inner ear originates from an embryonic ectodermal placode and rapidly develops into a three-dimensional structure (the otocyst) through complex molecular and cellular interactions. Many genes and their products are involved in inner ear induction, organogenesis, and cell differentiation. Retinoic acid (RA) is an endogenous signaling molecule that may play a role during different phases of inner ear development, as shown from pathological observations. To gain insight into the function of RA during inner ear development, we have investigated the spatio-temporal expression patterns of major components of RA signaling pathway, including cellular retinoic acid binding proteins (CRABPs), cellular retinoid binding proteins (CRBPs), retinaldehyde dehydrogenases (RALDHs), catabolic enzymes (CYP26s), and nuclear receptors (RARs). Although the CrbpI, CrabpI, and -II genes are specifically expressed in the inner ear throughout development, loss-of-function studies have revealed that these proteins are dispensable for inner development and function. Several Raldh and Cyp26 gene transcripts are expressed at embryological day (E) 9.0-9.5 in the otocyst and show mainly complementary distributions in the otic epithelium and mesenchyme during following stages. From Western blot, RT-PCR, and in situ hybridization analysis, there is a low expression of Raldhs in the early otocyst at E9, while Cyp26s are strongly expressed. During the following days, there is an up-regulation of Raldhs and a down-regulation for Cyp26s. Specific RA receptor (Rar and Rxr) genes are expressed in the otocyst and during further development of the inner ear. At the otocyst stage, most of the components of the retinoid pathway are present, suggesting that the embryonic inner ear might act as an autocrine system, which is able to synthesize and metabolize RA necessary for its development. We propose a model in which two RA-dependent pathways may control inner ear ontogenesis: one indirect with RA from somitic mesoderm acting to regulate gene expression within the hindbrain neuroepithelium, and another with RA acting directly on the otocyst. Current evidence suggests that RA may regulate several genes involved in mesenchyme-epithelial interactions, thereby controlling inner ear morphogenesis. Our investigations suggest that RA signaling is a critical component not only of embryonic development, but also of postnatal maintenance of the inner ear.

Aldehyde Oxidoreductases↗

PubMed2004

Restricted expression domains of Ezrin in developing epithelia of the chick.

Ezrin is a member of the ERM- (Ezrin-Radixin-Moesin-) family of actin binding proteins, which function as linkers of the cortical cytoskeleton to components of the plasma membrane. Additional roles for Ezrin in intracellular signalling and ion channel regulation were suggested. We found Ezrin mRNA in the anterior endo- and mesoderm of chick gastrula stage embryos. In these tissues Ezrin message is strongly expressed throughout early development of the foregut (pharynx) and heart tube. During later stages of development, highly restricted expression domains of Ezrin mRNA were detected in the endodermal lining of the pharyngeal pouches, the mesonephric duct and tubuli, and in the ectodermal placodes giving rise to the inner ear, eye lens and olfactory epithelium.

Animals↗

PubMed2004

Programmed cell death in the development of the vertebrate inner ear.

Programmed cell death is known to be an essential process for accurate ontogeny during the normal development of the inner ear. The inner ear is a complex sensory organ responsible for equilibrium and sound detection in vertebrates. In all vertebrates, the inner ear develops from a single ectodermic patch on the surface of the embryo's head, which undergoes a series of morphological changes to give rise to the complex structure of the adult inner ear. Enlargement and morphogenesis of the inner ear primordium is likely to depend on cellular division, growth, migration, differentiation and apoptosis. Here we describe the regions of programmed cell death that contribute to the final morphological aspect of the adult inner ear. The few studies that focus on the molecules that control this process during inner ear development indicate that the molecules and intracellular signaling pathways activated during the apoptotic response in the inner ear are similar to the previously described for the nervous system. In this review, we will describe some of the growth factors and key pathways that regulate pro- and anti-apoptotic signals and how they cross talk to determine the apoptotic or survival fate of cells in the development of the inner ear.

Animals↗

PubMed1989

Invagination of the otic placode: normal development and experimental manipulation.

The inner ear forms from paired ectodermal primordia that lie to either side of the developing hindbrain. Initially each primordium forms a shallow depression in the ectodermal surface. Invagination to form an otic pit coincides with the formation of several deep folds in the epithelial surface. An initial fold appears parallel to the embryonic axis and at the junction of the rhombencephalon with somitomeric mesoderm. This is followed by formation of cranial and caudal folds perpendicular to the axis and minor folds that are within the pit formed by earlier folding. The central region of the otic primordium remains in close apposition to the lateral surface of the neural tube during the process of fold formation, until the otic pit becomes quite deep. At that time, mesenchymal cells penetrate between the two layers. Experimental analysis of invagination supports the conclusion that otic invagination is controlled differently from that of similar organ primordia, such as the eye and thyroid. Whereas these other primordia can be stimulated to undergo normal morphogenetic shape changes precociously by treatments that presumably activate motile processes in the cytoskeleton, the same conditions have little effect on the otic placode. Similarly, neither inhibitors of calcium transport nor inactivators of calmodulin activity prevent otic pit formation, while these drugs block invagination of other primordia. These results suggest that otic invagination may be caused by changes in the surrounding tissues rather than by an activation of motility within the primordium.

Animals↗

PubMed2002

Fgf8 and Fgf3 are required for zebrafish ear placode induction, maintenance and inner ear patterning.

The vertebrate inner ear develops from initially 'simple' ectodermal placode and vesicle stages into the complex three-dimensional structure which is necessary for the senses of hearing and equilibrium. Although the main morphological events in vertebrate inner ear development are known, the genetic mechanisms controlling them are scarcely understood. Previous studies have suggested that the otic placode is induced by signals from the chordamesoderm and the hindbrain, notably by fibroblast growth factors (Fgfs) and Wnt proteins. Here we study the role of Fgf8 as a bona-fide hindbrain-derived signal that acts in conjunction with Fgf3 during placode induction, maintenance and otic vesicle patterning. Acerebellar (ace) is a mutant in the fgf8 gene that results in a non-functional Fgf8 product. Homozygous mutants for acerebellar (ace) have smaller ears that typically have only one otolith, abnormal semi-circular canals, and behavioral defects. Using gene expression markers for the otic placode, we find that ace/fgf8 and Fgf-signaling are required for normal otic placode formation and maintenance. Conversely, misexpression of fgf8 or Fgf8-coated beads implanted into the vicinity of the otic placode can increase ear size and marker gene expression, although competence to respond to the induction appears restricted. Cell transplantation experiments and expression analysis suggest that Fgf8 is required in the hindbrain in the rhombomere 4-6 area to restore normal placode development in ace mutants, in close neighbourhood to the forming placode, but not in mesodermal tissues. Fgf3 and Fgf8 are expressed in hindbrain rhombomere 4 during the stages that are critical for placode induction. Joint inactivation of Fgf3 and Fgf8 by mutation or antisense-morpholino injection causes failure of placode formation and results in ear-less embryos, mimicking the phenotype we observe after pharmacological inhibition of Fgf-signaling. Fgf8 and Fgf3 together therefore act during induction and differentiation of the ear placode. In addition to the early requirement for Fgf signaling, the abnormal differentiation of inner ear structures and mechanosensory hair cells in ace mutants, pharmacological inhibition of Fgf signaling, and the expression of fgf8 and fgf3 in the otic vesicle demonstrate independent Fgf function(s) during later development of the otic vesicle and lateral line organ. We furthermore addressed a potential role of endomesomerm by studying mzoep mutant embryos that are depleted of head endomesodermal tissue, including chordamesoderm, due to a lack of Nodal-pathway signaling. In these embryos, early placode induction proceeds largely normally, but the ear placode extends abnormally to midline levels at later stages, suggesting a role for the midline in restricting placode development to dorsolateral levels. We suggest a model of zebrafish inner ear development with several discrete steps that utilize sequential Fgf signals during otic placode induction and vesicle patterning.

Acridine Orange↗

PubMed2004

Specification of the otic placode depends on Sox9 function in Xenopus.

The vertebrate inner ear develops from a thickening of the embryonic ectoderm, adjacent to the hindbrain, known as the otic placode. All components of the inner ear derive from the embryonic otic placode. Sox proteins form a large class of transcriptional regulators implicated in the control of a variety of developmental processes. One member of this family, Sox9, is expressed in the developing inner ear, but little is known about the early function of Sox9 in this tissue. We report the functional analysis of Sox9 during development of Xenopus inner ear. Sox9 otic expression is initiated shortly after gastrulation in the sensory layer of the ectoderm, in a bilateral patch of cells immediately adjacent to the cranial neural crest. In the otic placode, Sox9 colocalizes with Pax8 one of the earliest gene expressed in response to otic placode inducing signals. Depletion of Sox9 protein in whole embryos using morpholino antisense oligonucleotides causes a dramatic loss of the early otic placode markers Pax8 and Tbx2. Later in embryogenesis, Sox9 morpholino-injected embryos lack a morphologically recognizable otic vesicle and fail to express late otic markers (Tbx2, Bmp4, Otx2 and Wnt3a) that normally exhibit regionalized expression pattern throughout the otocyst. Using a hormone inducible inhibitory mutant of Sox9, we demonstrate that Sox9 function is required for otic placode specification but not for its subsequent patterning. We propose that Sox9 is one of the key regulators of inner ear specification in Xenopus.

Animals↗

PubMed1999

Genomic organization and embryonic expression of the mouse fibroblast growth factor 9 gene.

Fibroblast growth factor 9 (FGF9), originally cloned as glial-activating factor from human glioma cells, is expressed in adult rat brain and kidney. Here we report the chromosomal localization, genomic organization, and embryonic expression pattern of the mouse Fgf9 gene. Fgf9 maps to chromosome 14 near the Ctla6 locus. The gene spans more than 34 kb and contains three exons and two introns. Translation initiation occurs in exon 1, and translation termination occurs in exon 3. Fgf9 RNA was detected during mouse embryogenesis in several tissues in which Fgf gene expression has not been previously described, including intermediate mesoderm of late-stage gastrulation, ventricular myocardium, lung pleura, skeletal myoblasts in the early limb bud, spinal cord motor neurons, olfactory bulb, and gut lumenal epithelium. Fgf9 is coexpressed with other Fgf genes in some skeletal myoblasts, in limb apical ectoderm, in craniofacial ectoderm, and in the retina, inner ear, and tooth bud. Dev Dyn 1999;216:72-88.

Amino Acid Sequence↗

PubMed2004

Mouse FGF15 is the ortholog of human and chick FGF19, but is not uniquely required for otic induction.

The inner ear develops from an ectodermal placode that is specified by inductive signals from the adjacent neurectoderm and underlying mesoderm. In chick, fibroblast growth factor (Fgf)-19 is expressed in mesoderm underlying the presumptive otic placode, and human FGF19 induces expression of otic markers in a tissue explant containing neural plate and surface ectoderm. We show here that mouse Fgf15 is the sequence homolog of chick and human Fgf19/FGF19. In addition, we show that FGF15, like FGF19, is sufficient to induce expression of otic markers in a chick explant assay, suggesting that these FGFs are orthologs. Mouse embryos lacking Fgf15, however, do not have otic abnormalities at E9.5-E10.5, suggesting that Fgf15 is not uniquely required for otic induction or early patterning of the otocyst. To compare FGF15 and FGF19 signaling components and assess where signals potentially redundant with FGF15 might function, we determined the expression patterns of Fgf15 and Fgf19. Unlike Fgf19, Fgf15 is not expressed in mesoderm underlying the presumptive otic placode, but is expressed in the adjacent neurectoderm. Fgfr4, which encodes the likely receptor for both FGF19 and FGF15, is expressed in the neurectoderm of both species, and is also expressed in the mesoderm only in chick. These results suggest the hypotheses that during otic induction, FGF19 signals in either an autocrine fashion to the mesoderm or a paracrine fashion to the neurectoderm, whereas FGF15 signals in an autocrine fashion to the neurectoderm. Thus, the FGFs that signal to the neurectoderm are the best potential candidates for redundancy with FGF15 during mouse otic development.

Animals↗

PubMed2003

The embryonic Octamer factor 3/4 displays distinct DNA binding specificity from those of other Octamer factors.

The Oct-3/4 is a transcriptional factor expressed rather specifically in inner cell mass and embryonic ectoderm during early embryogenesis in mammals. During the course of characterizing the regulatory element of embryonic transcriptional coactivator UTF1 which is one of the downstream genes of Oct-3/4, we have found that Oct-3/4, but not other Octamer factors, shows unique DNA binding specificity, being able to bind to variant Octamer sequence (5'-ACTAGCAT-3') present in UTF1 regulatory element. Here, we have determined the DNA binding property of Oct-3/4 in a systematic manner using all possible one point mutants of Octamer sequence as well as completely random sequences. These analyses led to the identification of nine distinct nucleotide sequences including the one (5'-ACTAGCAT-3') present in UTF1 regulatory element which serves rather as specific binding site for the Oct-3/4. Moreover, we show that, at least, one of the newly identified sequences, 5'-ATCAGCAT-3', exhibits a transcriptional stimulating activity equivalent to that of the variant Octamer sequence present in the UTF1 regulatory region in embryonic stem cells in a pluripotent-state specific manner.

Animals↗

PubMed1998

UTF1, a novel transcriptional coactivator expressed in pluripotent embryonic stem cells and extra-embryonic cells.

We have obtained a novel transcriptional cofactor, termed undifferentiated embryonic cell transcription factor 1 (UTF1), from F9 embryonic carcinoma (EC) cells. This protein is expressed in EC and embryonic stem cells, as well as in germ line tissues, but could not be detected in any of the other adult mouse tissues tested. Furthermore, when EC cells are induced to differentiate, UTF1 expression is rapidly extinguished. In normal mouse embryos, UTF1 mRNA is present in the inner cell mass, the primitive ectoderm and the extra-embryonic tissues. During the primitive streak stage, the induction of mesodermal cells is accompanied by the down-regulation of UTF1 in the primitive ectoderm. However, its expression is maintained for up to 13.5 days post-coitum in the extra-embryonic tissue. Functionally, UTF1 boosts the level of transcription of the adenovirus E2A promoter. However, unlike the pluripotent cell-specific E1A-like activity, which requires the E2F sites of the E2A promoter for increased transcriptional activation, UTF1-mediated activation is dependent on the upstream ATF site of this promoter. This result indicates that UTF1 is not a major component of the E1A-like activity present in pluripotent embryonic cells. Further analyses revealed that UTF1 interacts not only with the activation domain of ATF-2, but also with the TFIID complex in vivo. Thus, UTF1 displays many of the hallmark characteristics expected for a tissue-specific transcriptional coactivator that works in early embryogenesis.

Activating Transcription Factor 2↗

PubMed1990

XK endo B is preferentially expressed in several induced embryonic tissues during the development of Xenopus laevis.

XK endo B is a type I keratin that was originally identified by its preferential expression in the embryonic notochord of the amphibian Xenopus laevis. A peptide identical to a short region of its predicted amino acid sequence was used to generate antibodies against the XK endo B protein. This paper reports an immunocytochemical study of the spatial expression pattern of XK endo B during development. The protein was observed in the notochord and endoderm as predicted from previous RNA analysis. In addition, XK endo B was detected in the cement gland, in the pituitary, olfactory and pharyngeal pouch rudiments, and in a nonuniform distribution in the neural tube as well as the inner sensorial layer of the ectoderm. XK endo B expression is not limited to any germ layer or any particular cell type, but is nevertheless highly restricted in its distribution in the embryo. Its expression in several different embryonic tissues requiring inductive interactions for differentiation makes XK endo B a valuable tool with which to study the regulation of induced gene expression during embryogenesis.

Amino Acid Sequence↗

PubMed2004

Pax8 and Pax2a function synergistically in otic specification, downstream of the Foxi1 and Dlx3b transcription factors.

The vertebrate inner ear arises from an ectodermal thickening, the otic placode, that forms adjacent to the presumptive hindbrain. Previous studies have suggested that competent ectodermal cells respond to Fgf signals from adjacent tissues and express two highly related paired box transcription factors Pax2a and Pax8 in the developing placode. We show that compromising the functions of both Pax2a and Pax8 together blocks zebrafish ear development, leaving only a few residual otic cells. This suggests that Pax2a and Pax8 are the main effectors downstream of Fgf signals. Our results further provide evidence that pax8 expression and pax2a expression are regulated by two independent factors, Foxi1 and Dlx3b, respectively. Combined loss of both factors eliminates all indications of otic specification. We suggest that the Foxi1-Pax8 pathway provides an early 'jumpstart' of otic specification that is maintained by the Dlx3b-Pax2a pathway.

Animals↗

PubMed1989

Cell allocation and lineage in the early mouse embryo.

In the early mammalian embryo, initially asymmetric cell contacts appear to induce blastomere polarization, elements of which can persists through cytokinesis. This leads to the generation of inner and outer populations of blastomeres which may subsequently diverge as a result of residing in distinct microenvironments. Similar processes may account for the generation of primitive endoderm versus primitive ectoderm, and that of trophectoderm versus inner cell mass. However, if this is the case, the response of cells to positional cues must change as a function of either their previous positional history or the number of cycles they have completed. Once these primary tissues have been established, specific interactions between them lead to further cellular diversification.

Animals↗

PubMed1990

Development of cell surface activity and cell surface adhesiveness in early embryos of the newt, Cynops pyrrhogaster.

The development of cell surface activity and adhesiveness was examined in relation to cleavage number in early embryos of the newt, Cynops pyrrhogaster. Both large hyaline bleb formation and surface adhesiveness to substratum were manifested in presumptive ectodermal cells isolated from embryos after the eleventh cleavage (mid-blastula stage). Scanning electron microscopy of the inner surface of the blastocoelic wall (presumptive ectodermal cell layer) revealed the formation of large blebs after the eleventh cleavage. Treatment with alcian blue and lanthanum nitrate demonstrated the accumulation of an extracellular matrix (ECM) on the surface of large blebs.

Animals↗

PubMed2002

A review of inner ear fate maps and cell lineage studies.

A renewed interest in the development of the inner ear has provided more data on the fate and cell lineage relationships of the tissues making up this complex structure. The inner ear develops from a simple ectodermal thickening of the head called the otic placode, which undergoes a great deal of growth and differentiation to form a multichambered nonsensory epithelium that houses the six to nine sensory organs of the inner ear. Despite a large number of studies examining otic development, there have been surprisingly few fate maps generated. The published fate maps encompass four species and range from preotic to otocyst stages. Although some of these studies were consistent with a compartment and boundary model, other studies reveal extensive cell mixing during development. Cell lineage studies have been done in fewer species. At the single cell level the resulting clones in both chicks and frogs appear somewhat restricted in terms of distribution. We conclude that up until late placode stages there are no clear lineage restriction boundaries, meaning that cells seem to mix extensively at these early stages. At late placode stages, when the otic cup has formed, there are at least two boundaries located dorsally in the forming otocyst but none ventrally. These conclusions are consistent with all the fate maps and reconciles the chick and frog data. These results suggest that genes involved in patterning the inner ear may have dynamic and complex expression patterns.

Animals↗

PubMed2004

Fates of mouse embryonic stem cells transplanted into the inner ears of adult mice and embryonic chickens.

The potential of embryonic stem (ES) cells to differentiate into inner ear hair cells was examined in this study. Undifferentiated mouse ES cells transplanted into neomycin-damaged mouse inner ears were evaluated by immunohistochemistry 4 weeks after transplantation. Some ES cells were positive for E-cadherin or NCAM, and most transplanted cells were positive for SSEA3 and Ki67. None were positive for Myosin VIIa or MF20. These results indicate that the damaged inner ear may have some activity inducing ES cells to develop into ectoderm cells, but the effect was insufficient to induce inner ear hair cells. Next, SDIA/BMP-treated ES cells were transplanted into embryonic chicken inner ear rudiments. Embryonic chickens were expected to share the same developmental systems as mice. SDIA/BMP treatment drove ES cells to the population including neural crest cells and probably placode cells ES colonies were found next to or in the otic vesicles but were not a part of vesicle walls, indicating that transplanted ES cells could not be expected to be the same kind of cells as chicken otic vesicle cells Some ES colonies were found at the vestibulo-cochlear ganglions. To induce inner ear hair cells in this system, the competency of ES cells and otic induction signals should be defined further.

Animals↗