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PubMed1998

Anterior structural defects by misexpression of Xgbx-2 in early Xenopus embryos are associated with altered expression of cell adhesion molecules.

The RNA of the noncluster homeobox gene, Xgbx-2, is localized during neurulation to a narrow band of tissue at the midbrain hindbrain boundary (anterior hindbrain). The localized expression of Xgbx-2 within the nervous system prompted us to assess its function during early development by injection of synthetic Xgbx-2 RNA into the animal pole region of both dorsal blastomeres at the four-cell stage. Injection of Xgbx-2 RNA leads to dose-dependent alterations in anterior dorsal structures. These defects include abnormal eye development including reduced and missing eyes, reduced or missing cement glands, and abnormal brain development. Additionally, coinjection with lineage label (either beta-galactosidase or green fluorescent protein) shows there is a dose-dependent misplacement of cells. These misplaced cells can be found in such locations as the blastocoele, gastrocoele, or ventricles in the brain. In some spawnings, misplaced cells are expelled from the embryo into the periviteline space. In general, the phenotype of Xgbx-2 RNA-injected embryos is strikingly similar to the phenotypes observed when dominant-negative RNA constructs of Ca2+-dependent cell-adhesion molecules are injected into similar regions of early embryos. Xgbx-2 misexpression enhanced the dissociation of animal hemisphere cells, and inhibited Ca2+-dependent cell adhesion in dissociated animal hemisphere cells in vitro. Additionally, when the expression of various calcium-dependent cadherins was tested, it was shown that misexpression of Xgbx-2 prevents N-cadherin expression during early neurulation. These observations suggest that the transcription factor, Xgbx-2, functions normally in the regionalization of the neural tube (specifically the anterior hindbrain) by regulating differential cell adhesion and subsequently cell identity.

Animals↗

PubMed1998

The superposition of a temporally incoherent magnetic field inhibits 60 Hz-induced changes in the ODC activity of developing chick embryos.

Previously, we have shown that the application of a weak (4 microT) 60 Hz magnetic field (MF) can alter the magnitudes of the ornithine decarboxylase (ODC) activity peaks which occur during gastrulation and neurulation of chick embryos. We report here the ODC activity of chick embryos which were exposed to the superposition of a weak noise MF over a 60 Hz MF of equal (rms strength). In contrast to the results we obtain with a 60 Hz field alone, the activity of ODC in embryos exposed to the superposition of the incoherent and 60 Hz fields was indistinguishable from the control activity during both gastrulation and neurulation. This result adds to the body of experimental evidence which demonstrates that the superposition of an incoherent field inhibits the response of biological systems to a coherent MF. The observation that a noise field inhibits ODC activity changes is consistent with our speculation that MF-induced ODC activity changes during early development may be related to MF-induced neural tube defects at slightly later stages (which are also inhibited by the superposition of a noise field).

Animals↗

PubMed1994

Formation and patterning of the avian neuraxis: one dozen hypotheses.

Formation of the neuraxis is dependent on cell-cell interactions and cell movements beginning during stages of gastrulation. Cell movements bring together new combinations of cells, allowing sequential inductive interactions to occur and leading to the specification of the neural plate and to its ultimate mediolateral (subsequently dorsoventral) and rostrocaudal patterning. Formation of the neural plate involves changes in the shape of its constituent cells and the first appearance of neural-specific cell markers. Shortly after the neural plate forms it undergoes 'shaping', in which the pseudostratified columnar epithelium constituting the neural plate thickens apicobasally, narrows transversely and extends longitudinally. Shaping is driven by three principal intrinsic types of cell behaviour: changes in cell shape, position and number. The next stage of neurulation begins while shaping is underway--bending of the neural plate. Bending involves two main processes, furrowing and folding. Furrowing of the neural plate is associated with the formation of the hinge points; these are localized, longitudinal areas where the neuroepithelium is attached to adjacent tissues and where wedging of neuroepithelial cells occurs. Cell wedging in the median hinge point occurs as a result of inductive interactions with the notochord; such wedging drives furrowing, thereby facilitating subsequent folding. Folding of the neural plate requires extrinsic forces generated largely by the surface ectoderm. Types of cell behaviour that could provide such forces include changes in cell shape, position and number. As a result of shaping and bending of the neural plate, the neural folds are brought into apposition in the dorsal midline. Final closure of the neural groove is mediated by cell surface glycoconjugates coating the apical surfaces of the neural folds. Patterning of the neuraxis begins during shaping of the neural plate and continues throughout stages of neurulation and into early postneurula stages. Patterning probably involves inductive interactions with adjacent tissues and the expression of putative positional identity genes such as homeobox-containing genes.

Animals↗

PubMed1980

Characterization of intercellular junctions in the caudal portion of the developing neural tube of the chick embryo.

The types of intercellular junctions present within caudal levels of the chick neural tube (i.e., future lower thoracic and lumbosacral regions of the spinal cord) were determined by freeze-fracture of stage 14 to 16 embryos. Two levels of the developing neural tube were examined: the region of the neurulation overlap zone--consisting of primary neural tube dorsally and secondary neural tube ventrally--and the portion of the primary neural tube located just cranial to the overlapping region. Gap junctions were the most numerous type of intercellular junction present within the primary neural tube. These junctions were located primarily in juxtaluminal areas, near the apices of neuroepithelial cells, and sometimes also at the bases of these same cells. In addition, focal, poorly defined tight junctions occasionally occupied juxtaluminal regions of the primary neural tube. The medullary cord (i.e., the immediate precursor of the secondary neural tube) and secondary neural tube contained gap junctions exclusively. Gap junctions were first found in these areas at the lateral borders of the medullary cord, concomitant with formation of this structure, and then at the interface between the elongated, peripheral cells of the cord and the irregularly shaped and loosely arranged central cells of this structure. Finally, gap junctions were distributed radially around secondary lumina formed by cavitation. The precise spatial and temporal correlation between the appearance of gap junctions and the specific changes occurring in cellular morphology and arrangement during secondary neurulation strongly suggest that gap junctions may have a role in coordinating cellular activities during formation of both the medullary cord and the secondary neural tube.

Animals↗

PubMed1992

Pattern of expression of transforming growth factor-beta 4 mRNA and protein in the developing chicken embryo.

Expression of TGF-beta 4 mRNA and protein was studied in the developing chicken embryo using specific cDNA probes and antibodies for chicken TGF-beta 4. Expression of TGF-beta 4 mRNA was detected by day 4 of incubation (Hamburger and Hamilton stage 22, E4) by RNA Northern blot analysis and increased with developmental age until day 12 of incubation (stage 38, E12) where it was detected in every embryonic tissue examined, with expression being highest in smooth muscle and lowest in the kidney. The steady-state level of expression of TGF-beta 4 mRNA remained relatively constant in most embryonic tissues through day 19 (stage 45, E19). In situ hybridization analysis detected TGF-beta 4 mRNA as early as the "definitive primitive streak" stage (stage 4); during neurulation (stage 10), TGF-beta 4 mRNA was detected in all three germ layers, including neuroectoderm. Following neurulation, TGF-beta 4 mRNA was detected in the neural tube, notochord, ectoderm, endoderm, sclerotome, and myotome, but not dermotome at stage 16. By day 6 of incubation (stage 29, E6), TGF-beta 4 mRNA was localized in several tissues including heart, lung, and gizzard. Immunohistochemical staining analysis also showed expression of TGF-beta 4 protein in all three germ layers as early as stage 4 in various cell types in qualitatively similar locations as TGF-beta 4 mRNA. These results suggest that TGF-beta 4 may play an important role in the development of many tissues in the chicken.

Animals↗

PubMed2005

Embryology of neural tube development.

Neurulation is the process of forming the neural tube, which will become the brain and spinal cord. This article reviews the various cellular processes involved in neurulation and discusses possible roles of folate in this process.

Animals↗

PubMed1987

Cell cycle and neuroepithelial cell shape during bending of the chick neural plate.

Neuroepithelial cells change shape from spindle-like to wedge-like within three restricted areas (hinge points) of the bending neural plate. The mechanisms underlying these localized cell shape changes and the specific role that these changes play in bending are unclear. This study was designed to determine whether changes in neuroepithelial cell shape involve basal cellular expansion owing to alteration of the cell cycle. Neurulating chick embryos were treated with colchicine to arrest and accumulate cells in metaphase, and colchicine indices and cell generation times were calculated for the neural plate. During bending of the neural plate, cell generation time in the median hinge point, which contains predominantly wedge-shaped cells, was significantly longer than that in adjacent lateral areas of the neural plate, which contain predominantly spindle-shaped cells. In addition, cell generation time in the flat neural plate, which contains predominantly spindle-shaped cells and has not yet differentiated into the median hinge point and lateral subdivisions, was identical to that in lateral areas of the bending neural plate but was significantly shorter than that in the median hinge point. These results support the hypothesis that changes in neuroepithelial cell shape from spindle-like to wedge-like involve basal cellular expansion owing to alteration of the cell cycle. Additional tests of this hypothesis and studies on the role of localized cell shape changes in neurulation are in progress.

Animals↗

PubMed1993

Immunocytochemical analysis of a novel carbohydrate differentiation antigen (CDA-3C2) associated with olfactory and otic systems during embryogenesis in the rat.

Carbohydrate differentiation antigens are known to display specific patterns of expression during mammalian development and are thought to participate in significant morphogenetic events. In the present study, two monoclonal antibodies that react with a novel carbohydrate differentiation antigen (CDA-3C2) were used to analyze, by light microscopy, the spatiotemporal distribution of this unique high molecular weight antigen during embryogenesis in the rat. Correlative analysis of the development of peripheral neural structures, in which CDA-3C2 was expressed, was carried out with an anti-neurofilament antibody. Enzymatic digestion, combined with Western blots, reveal that the CDA-3C2 epitope is a carbohydrate which is carried on a high molecular weight glycoprotein with a mass of greater than 1 million Daltons. Characteristic of carbohydrate antigens, immunoreactivity was found in several distinct cellular patterns: only along the apical border of cells, along lateral and basal membranes of cells, and extracellular-like staining in the mesenchyme. During neurulation, CDA-3C2 showed differential staining in the ectoderm, distinguishing lateral from neural regions. Following closure of the neural tube, there was a striking specificity of expression of CDA-3C2 in the periphery, found almost exclusively in olfactory and otic epithelial structures. While CDA-3C2 is found in placode-derived tissues that subserve sensory transduction, it appears to be primarily associated with the supportive cells (and their secretions) in both otic and olfactory regions and less so with the sensory cells. The data suggest that a unique carbohydrate antigen on a large macromolecule may play a role in neurulation and/or morphogenesis of the placode-derived otic and olfactory structures.

Animals↗

PubMed2002

Multistep role for actin in initial closure of the mesencephalic neural groove in the chick embryo.

In a previous study, we have demonstrated that initial closure of the mesencephalic neural groove in the chick embryo is different from neurulation elsewhere. The neural groove invaginates, the walls appose and make contact in a ventrodorsal direction, and subsequently separate ventrally, forming an incipient neural tube lumen, which finally widens into a definitive lumen. In this study, a role for actin in the processes of this initial mesencephalic closure is studied. Based on rhodamine-phalloidin-stained sections, three distinct actin distribution patterns emerged, and time-lapse video microscopy revealed cytochalasin-D-reversible neurulation movements. We propose that actin is involved in formation and stabilization of the neural groove hinge point, in invagination of dorsal neuroepithelial cells into the neural groove, in the origin of the incipient lumen and the reinforcement of adhesion of the dorsal neural folds, and finally in the development of a wide lumen. Such a multifunctional effect of actin microfilaments within a narrow time window and at specific sites has not been reported yet.

Actins↗

PubMed2005

Origin, fate, and function of the components of the avian germ disc region and early blastoderm: role of ooplasmic determinants.

In the avian oocytal germ disc region, at the end of oogenesis, we discerned four ooplasms (alpha, beta, gamma, delta) presenting an onion-peel distribution (from peripheral and superficial to central and deep. Their fate was followed during early embryonic development. The most superficial and peripheral alpha ooplasm plays a fundamental role during cleavage. The beta ooplasm, originally localized in the peripheral region of the blastodisc, becomes mainly concentrated in the primitive streak. At the moment of bilateral symmetrization, a spatially oblique, sickle-shaped uptake of gamma and delta ooplasms occurs so that gamma and delta ooplasms become incorporated into the deeper part of the avian blastoderm. These ooplasms seem to contain ooplasmic determinants that initiate either early neurulation or gastrulation events. The early neural plate-inducing structure that forms a deep part of the blastoderm is the delta ooplasm-containing endophyll (primary hypoblast). Together with the primordial germ cells, it is derived from the superficial centrocaudal part of the nucleus of Pander, which also contains delta ooplasm. The other structure (gamma ooplasm) that is incorporated into the caudolateral deep part of the blastoderm forms Rauber's sickle. It induces gastrulation in the concavity of Rauber's sickle and blood island formation exterior to Rauber's sickle. Rauber's sickle develops by ingrowth of blastodermal cells into the gamma ooplasm, which surrounds the nucleus of Pander. Rauber's sickle constitutes the primary major organizer of the avian blastoderm and generates only extraembryonic tissues (junctional and sickle endoblast). By imparting positional information, it organizes and dominates the whole blastoderm (controlling gastrulation, neurulation, and coelom and cardiovascular system formation). Fragments of the horns of Rauber's sickle extend far cranially into the lateral quadrants of the unincubated blastoderm, so that often Rauber's sickle material forms three quarters of a circle. This finding explains the regulative capacities of isolated blastoderm parts, with the exception of the anti-sickle region and central blastoderm region, where no Rauber's sickle material is present. In avian blastoderms, there exists a competitive inhibition by Rauber's sickle on the primitive streak and neural plate-inducing effects of sickle endoblast. Avian primordial germ cells contain delta ooplasm derived from the superficial part of the nucleus of Pander. Their original deep and central ooplasmic localization has been confirmed by the use of a chicken vasa homologue. We conclude that the unincubated blastoderm consists of three elementary tissues: upper layer mainly containing beta ooplasm, endophyll containing delta ooplasm, and Rauber's sickle containing gamma ooplasm). These elementary tissues form before the three classic germ layers have developed.

Animals↗

PubMed2006

Apical localization of ASIP/PAR-3:EGFP in zebrafish neuroepithelial cells involves the oligomerization domain CR1, the PDZ domains, and the C-terminal portion of the protein.

Neurulation in zebrafish (Danio rerio) embryos is characterized by oriented cell divisions and the progressive establishment of cellular polarity. Mitoses in the neural plate and neural tube are planar, but in the neural keel/rod stage, the mitotic spindle rotates by 90 degrees, causing cell divisions to occur perpendicular to the plane of the neuroepithelium. The mechanisms and molecules that establish cellular polarity and cause the stereotypic orientation of the mitotic spindle during neurulation are largely unknown. In Caenorhabditis elegans and Drosophila, the PAR/aPKC complex has been shown to be involved in both establishment of cellular polarity and spindle orientation. Here, we show that the conserved N-terminal oligomerization domain (CR1) and the PDZ domains of ASIP/PAR-3:EGFP are involved in its localization to the apical membrane in zebrafish neuroepithelial cells. We further show that the C-terminal part of ASIP/PAR-3 contributes to proper localization and that the apical localization signals in ASIP/PAR-3 prevent the basolateral localization of a Numb:PAR-3 fusion protein. The parallel orientation of the mitotic spindle in the neural tube, however, is only weakly impaired upon overexpression of various ASIP/PAR-3:EGFP constructs.

Amino Acid Sequence↗

PubMed2006

Expression analysis of IGFBP-rP10, IGFBP-like and Mig30 in early Xenopus development.

To date, five members of the insulin-like growth factor-binding protein (IGFBP) superfamily have been described in Xenopus laevis. Here, we report the isolation of two new IGFBPs: xIGFBP-rP10, and xIGFBP-like. The proteins share the same domain architecture, and together with Mig30, form a subgroup within the IGFBP superfamily. Temporal expression analysis shows that they are expressed differentially during early development. xIGFBP-rP10 is continuously expressed, whereas Mig30 expression peaks during gastrulation. IGFBP-like is expressed from neurulation onward. The three genes have characteristic spatial expression domains, which overlap in some regions. Both xIGFBP-rP10 and Mig30 are expressed on the dorsal side of the embryo during gastrulation. Later, xIGFBP-rP10 is expressed in the notochord, the floor plate, the somites, and the fin. xIGFBP-like expression is seen primarily in the developing central nervous system and overlaps with Mig30 expression at the end of neurulation in the developing somites and in tail bud stages in the eyes.

Amino Acid Sequence↗

PubMed1995

Two isoforms of Xenopus retinoic acid receptor gamma 2 (B) exhibit differential expression and sensitivity to retinoic acid during embryogenesis.

We report the isolation of two retinoic acid receptor isoforms (RAR gamma), which differ only in the 5'untranslated and putative N-terminus A regions. The two isoforms appear to serve as early markers for the presumptive neural axis; however, their expression patterns differ. RAR-gamma 2.1 is first expressed at gastrulation at the dorsal lip and subsequently along the presumptive neural axis. RAR- gamma 2.2 represents the full-length sequence of a receptor cDNA already partially characterized and present as a maternal transcript [Ellinger-Ziegelbauer and Dreyer (1991); Genes Dev 5:94-104, (1993): Mech Dev 41:31-46; Pfeffer and DeRobertis, (1994) Mech Dev: 45:147-153]. Unlike RAR-gamma 2.2, the 2.1 variant is not expressed either in pre-somitic mesoderm or notochord. RAR-gamma 2.1 is strongly expressed in branchial arches and to a lesser extent in the neural floor plate. The two isoforms also exhibit differential sensitivity to retinoic acid. Constitutive expression of RAR gamma 2.2 following neurulation appears to be depressed by treatment with retinoic acid, but domains of highest expression, namely, the head and tail, remain relatively unaffected, as do patterns of expression prior to late neurulation. By contrast, RAR-gamma 2.1 is not transcribed in retinoid-inhibited structures. Using microinjection techniques, we show that changes of RAR-gamma 2.1 expression in presumptive head structures occur as an early and local consequence of retinoic acid administration. Since RAR-gamma 2.1 expression is inhibited by retinoic acid, we tested to see if other treatments that perturb axis formation had any effect. Surprisingly, UV irradiation did not suppress that its inhibition by retinoic acid is not due solely to inhibition of anterior neural development. These experiments demonstrate a new subdivision of isoforms that undergo differential expression during development and that exhibit differential sensitivity to retinoic acid and to UV. This sensitivity and the presence of this isoform variant in regions that are known to exhibit polarizing activity strengthen the hypothesis that these receptors play a primary role during morphogenesis.

Amino Acid Sequence↗

PubMed1990

Expression of the Axd (axial defects) mutation in the mouse is insensitive to retinoic acid at low dose.

The Axd mutation in the mouse acts by an unknown mechanism to cause lumbosacral open neural tube defects and a variety of tail anomalies. Retinoic acid (RA) plays a number of different physiological and developmental roles and has been shown to affect neurulation in mice and other species. Indeed, reports have shown that this biologically active compound (or its metabolites) at low dose can alter the incidence of neural tube defects (NTD) in curly-tail (ct), splotch (Sp), and delayed splotch (Spd) mice, strains that are genetically predisposed to such abnormalities. The aim of the present study was to determine if RA administered under similar conditions would affect the penetrance or expression of the Axd mutation or survival of Axd homozygotes. Axd/+ and +/+ dams were exposed to RA intraperitoneally (5 mg/kg) on D9 postcoitus. No difference in incidence or extent of neural tube defects or other axial anomalies was detected among embryos of Axd/+ dams given RA compared with those administered vehicle only. This finding is consistent with the diversity of gene-controlled steps required for neurulation and the differing sensitivities of specific mutants to rescue by extrinsic agents.

Animals↗

PubMed2003

Competitive inhibition by Rauber's sickle of the primitive streak and/or (pre)neural plate inducing effects of sickle endoblast in avian blastoderms.

When in unincubated chicken blastoderms the Rauber's sickle is (sub)totally mechanically removed by selective scraping, the further evolution of the blastoderm in culture is often profoundly disturbed, going from only expansion of the upper layer and preneural plate formation to the development of a slowly growing miniature embryo. Our results suggest that the developmental potencies of the embryo are related to the presence or absence of Rauber's sickle material left after its removal. This can be checked after culture by the presence or nonpresence of junctional endoblast (derived from Rauber's sickle) and the concomitant induction of blood islands in the immediate neighborhood. Our study thus indicates that without Rauber's sickle (in the cases of successful total selective removal), an avian blastoderm cannot develop normally, even in the presence of an intact caudal marginal zone. After placing a fragment of quail sickle endoblast on the anti-sickle region of unincubated chicken blastoderms from which the Rauber's sickle was (sub)totally removed, different developmental scenarios were seen, according to the degree of removal, both in the anti-sickle as in the sickle regions. 1) If Rauber's sickle activity is strongly reduced, then besides a centripetally directed miniature embryo, induced by the remnants of the autochthonous Rauber's sickle, an additional centripetally directed embryo or preneural plate (without accompanying blood islands) develops in the anti-sickle region under inductory influence of the apposed quail sickle endoblast. We make a distinction between a neural plate and a preneural plate. The latter consists of a thickening of the upper layer (with the same initial aspect as a neural plate) adjacent to endophyll or sickle endoblast in the absence of chordomesoblast and gastrulation phenomena. 2) If Rauber's sickle activity is totally absent, then the inducing power of the sickle endoblast fragment becomes maximal and, starting from the anti-sickle region, one single embryo (without blood islands) extending over the whole area centralis appears. 3) If much of the Rauber's sickle material has been left in the blastoderm, then the inducing activity of the sickle endoblast, placed on the anti-sickle region, will be totally suppressed (although the sickle endoblast remains intact) and neither a preneural plate nor a primitive streak was induced. After placing a fragment of quail sickle endoblast on the anti-sickle region of an unincubated chicken blastoderm from which the Rauber's sickle and surrounding tissues were completely excised, an embryo was always induced by the sickle endoblast in the adjacent upper layer of this anti-sickle region. In the absence of sickle endoblast, this never occurred. Thus, our experiments demonstrate that in the absence of the Rauber's sickle, a parent tissue (sickle endoblast) induces both gastrulation and neurulation phenomena, while in the full presence of Rauber's sickle these functions are totally suppressed. Moreover, Rauber's sickle not only organizes gastrulation and blood island formation by itself but also influences neurulation at a distance (in space and time) by part of its cell lineage (i.e., sickle endoblast). Our study suggests that the inhibitory effect of Rauber's sickle on its parent tissue (sickle endoblast) represents an early mechanism impairing polyembryony, so that only a single primary major organizer (Rauber's sickle) remains active in the young avian germinal disc.

Animals↗

PubMed2004

Induction and improved embryonic development by the nucleus of Pander in associated avian blastoderm parts: influence of delta or gamma ooplasm.

After placing in vitro, central subgerminal ooplasm (containing a central nucleus of Pander) from a quail germ disc of a prelaid egg (before symmetrization) on the upper layer of an isolated chicken antisickle, we observed the induction of a radially oriented preneural plate (without interference of chordamesoblast). This observation suggests the primary existence during the period of symmetrization in utero of an until now unknown temporospatially linked "vertical" effect, emanating from the nucleus of Pander, on the parallel (pre)neural plate anlage forming part of the area centralis in the overlying blastoderm. For comparison, we "sandwiched" in vitro a quail sickle endoblast fragment between the deep side of the upper layer of an isolated chicken antisickle region and a central subgerminal ooplasmic mass. This resulted in a colonization of the subgerminal ooplasmic mass by quail sickle endoblast cells followed by improved neurulation and/or gastrulation phenomena. The latter never occurs in the absence of central subgerminal ooplasm. In both types of experiments there seems to exist a common link between the observed induction phenomena: the presence of delta ooplasm in the involved deep structures. Indeed, the nucleus of Pander contains delta ooplasm as well as the structures derived from it, i.e., endophyll with primordial germ cells and sickle endoblast-derived cells after colonization of the neighboring central ooplasm (present study). Therefore, we think that the preneural plate-inducing effect observed after placing a nucleus of Pander on the antisickle region is due to the presence of a factor in the delta ooplasm that diffuses in the neighborhood. The appearance of gastrulation phenomena in the second type of experiment seems to be due to colonization of the more peripheral part of the central subgerminal ooplasm containing the more superficial and peripheral gamma ooplasm in which Rauber's sickle material can develop. This suggests that the kind of involved ooplasm (delta or gamma) can predetermine the inductive activity of the deep structures that contain it: the central part of the nucleus of Pander and/or endophyll for preneurulation phenomena and sickle endoblast (in the presence of central subgerminal ooplasm) for gastrulation and/or neurulation phenomena.

Animals↗

PubMed1993

IGF-I and the IGF-I receptor in development of nonmammalian vertebrates.

Extracellular signals are likely to be involved in the control of growth and differentiation during embryogenesis of vertebrates. These signals include, among others, several members of the insulin family: insulin-like growth factor (IGF)-I, IGF-II, and insulin. In the chick embryo, maternal IGF-I is stored in the yolk. In addition, the embryonic IGF-I gene is expressed very early and in late development in multiple tissues. We have used reverse-transcribed (RT) RNA and amplification by the polymerase chain reaction (PCR) to detect IGF-I gene expression. IGF-I was preferentially expressed in cephalic regions during late neurulation and early organogenesis. During late organogenesis, in some tissues, such as the eye lens, IGF-I gene expression is compartmentalized to a subset of cells, the epithelial cells. In these lens cells, IGF-I stimulates transcription of the delta-crystallin gene. Competence to respond to IGF-I exists in multiple cell types, since, based on binding studies, receptors for IGF-I are widespread in the gastrulating and neurulating embryo. Target tissues in which an autocrine/paracrine role for IGF-I appears more likely are the developing eye lens and retina, which are avascular organs rich in IGF-I receptors. In late development, IGF-I may have an additional endocrine role, with an impact on the general growth of the chick embryo. In embryos developed ex ovo, that show growth retardation after day 10 of embryogenesis, IGF-I serum levels are very low. By day 8, expression of IGF-I mRNA in these embryos is markedly reduced in multiple tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2002

Determination of the embryonic inner ear.

Inner ear induction, like induction of other tissues examined in recent years, is likely to be comprised of several stages. The process begins during gastrulation when the ectoderm is competent to respond to induction. It appears that a signal from the endomesoderm underlying the otic area during gastrulation initiates induction complemented by a signal from presumptive neural tissue. By the neural plate stage, a region of ectoderm outside the neural plate is "biased" toward ear formation; this process may be part of a more general "placodal" bias shared by several sensory tissues. Induction continues during neurulation when a signal from neural tissue (possibly augmented by mesoderm underlying the otic area) results in ectoderm committed to otic vesicle formation at the time of neural tube closure. Studies on several gene families implicate them in the ear determination process. Fibroblast Growth Factor (FGF) family members are clearly involved in induction: FGFs are appropriately expressed for such a role, and have been shown to be essential for inner ear development. FGFs also have inductive activity, although it is not clear if they are sufficient for ear induction. Activation of transcription factors in the otic ectoderm, for example, by Pax gene family members, provides evidence for important changes in the responding ectoderm beginning during gastrulation and continuing through specification at the end of neurulation, although few functional tests have defined the role of these genes in determination. The challenge remains to merge embryologic data with gene function studies to develop a clear model for the molecular basis of inner ear induction.

Animals↗