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Fetuin as a marker of cortical plate cells in the fetal cow neocortex: a comparison of the distribution of fetuin, alpha 2HS-glycoprotein, alpha-fetoprotein and albumin during early development.

Fetuin, alpha 2HS-glycoprotein (alpha 2HS), alpha-fetoprotein (AFP) and albumin have been shown to be present in some regions of the neocortex in two early stages of development of the cow brain using PAP immunocytochemistry. In the pre-cortical plate stage fibres of the primordial plexiform layer stained positively for fetuin. No staining was seen for albumin but plasma and cerebrospinal fluid (CSF) were positive for alpha 2HS and AFP. In the early cortical plate stage the strongest fetuin positive staining was seen in the earliest formed cells of the plate. alpha 2HS staining was much less intense but similar in distribution. The possible role of fetuin, or related glycoproteins, in cortical plate differentiation is discussed. Staining for AFP and for albumin was seen mainly in the ventricular zone and marginal zone fibres, and had a similar distribution and intensity for both proteins. Plasma and CSF stained for all four proteins. Tests showed some cross-reactivity between fetuin and anti-alpha 2HS and, to a much lesser extent, between antisera to AFP and albumin and antigens denatured by fixation.

Animals↗

Cell-specific accumulation of Drosophila proteasomes (MCP) during early development.

The proteasome (MCP) is a high relative molecular mass multicatalytic proteinase complex composed of nonidentical protein subunits. We have investigated the cellular distribution of the enzyme complex during Drosophila embryogenesis using the proteasome specific antibodies N19-35 and N19-28 for immunocytology. Antibody staining of whole-mount embryos shows that during embryogenesis proteasomes are present in proliferating cells and that their accumulation and turnover is differentially regulated. Our data suggest that the proteasome may serve different proteolytic processes and that the enzyme may be involved in cell-specific proteolytic events required for cell proliferation and morphogenesis during early Drosophila development.

Animals↗

Graphical simulation of early development of the cerebral cortex.

Much experimental data exists concerning the development of the cerebral cortex. There is a need for a common vehicle to integrate this data and to allow the testing of hypotheses concerning development. Computer simulation and visualization are powerful mechanisms for hypothesis testing. Our long-term goal is to create a robust, extensible, portable tool for simulation and visualization of cortical development to serve both research and educational purposes. This paper describes a simulation program, SimCortex, which models the early stages of development of the cerebral cortex of the mouse. Version 1.0 of SimCortex models the proliferation of progenitor cells in the pseudostratified ventricular epithelium (PVE), the generation of young neurons and their migration into the cortical plate, which is the forerunner of cell layers II through VI of the adult cortex. We present an overview of the design and implementation of SimCortex, sample output of the system and a comparison of our results with experimental data. We conclude with a brief overview of proposed future enhancements of the system.

Animals↗

[The early development of the Jacobson's organ in the cat (Felis silvestris)].

The histological study of the nose of an embryo of the cat (Felis silvestris 10 mm) presents a simple cavity which caudally communicates with the oral cavity by a narrow cleft, the primitive choana. This aperture results from the former rupture of the membrana bucconasalis of which the present material still contains remnants. Compared to the simple nasal cavity, the organ of Jacobson, situated at the base of the broad fetal nasal septum, shows a progressive development. From this one might conclude, according to ontogenetical rules, an early functional importance of the accessory olfactory organ. The currently fetal nose under investigation presents the organ as a primary open groove which increases in depth from rostral to caudal. Only caudally, a short section of the organ is already formed into a tube. From the functional point of view, the epithelial lining of this organ is still undifferentiated, but its dorsal part is clearly thickened. It seems that this indicates an early arrangement of the later olfactory epithelium. Beside this it is striking that in early fetal life, the organ of Jacobson extends to a remarkable length within the nasal cavity. Obviously the organ occupies, early in ontogeny, its area inside the little developed nose. Finally, the striking resemblance of the topography of the organ of Jacobson between early embryos of mammals and those of fetal and even some adult reptiles is discussed.

Animals↗

Dead cells can be phagocytosed by any neighboring cell in early developing rat brain.

We investigated phagocytosis in vitro, on tissue samples of rat brain from 10th to 18th embryonic days. Our results show that, in the early stage of development, degenerated cells can be phagocytosed by any neighboring cell in the brain. The phagocytosing cells were of the same type as the others and did not resemble microglia in the samples obtained from 10th to 14th embryonic days. In embryonic rat brain microglial cells have been reported to appear after the 12th day, while phagocytosing cells were already observed in our 10- and 12-day materials as well. The general ability of embryonic rat brain cells to phagocytose is further supported by the results of horseradish peroxidase studies. Typical microglial cells could be observed in our 16- and 18-day materials. On the basis of our results we do not intend to modify the notion on the origin of microglia. Our concept is that the microglia gradually replaces the multipotential cells of the embryonic brain in their "cleaning-off" function as the differentiation of these latter cells progresses.

Animals↗

Isolation of the Xenopus homolog of int-1/wingless and expression during neurula stages of early development.

We have isolated the Xenopus homolog (Xint-1) of the mouse protooncogene int-1 from a neurula stage 17 cDNA library. The deduced protein sequence of Xint-1 includes 371 amino acids. The Xint-1 protein is more similar to the mammalian int-1 product (69%), than to the Drosophila counterpart of int-1, wingless (50%). Xint-1 shares several characteristics of secreted proteins with the other int-1 homologs: it has a hydrophobic leader, multiple conserved potential N-linked glycosylation sites and is rich in cysteine residues. All 23 cysteines are conserved in the three proteins. Xint-1 is transiently expressed during the neurula stages of early Xenopus development.

Amino Acid Sequence↗

Polymorphism in ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene (ENPP1/PC-1) and early development of advanced diabetic nephropathy in type 1 diabetes.

A polymorphism in the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene (ENPP1) (previously known as PC-1), resulting in an amino acid change from lysine to glutamine at codon 121 (K121Q), is associated with insulin resistance. A small follow-up study of patients with type 1 diabetes and proteinuria found that renal function declines more rapidly in carriers of the Q variant than in noncarriers. To examine this finding further, we conducted a large case-control study and a family-based study. Genomic DNA was obtained from 659 patients: 307 with normal urinary albumin excretion despite diabetes duration of >15 years (control subjects) and 352 with advanced diabetic nephropathy, of whom 200 had persistent proteinuria and 152 had end-stage renal disease (ESRD). Individuals were genotyped for Q and K variants using a previously described protocol. The frequency of Q variant carriers was 21.5% in control subjects, 31.5% in subjects with proteinuria, and 32.2% in subjects with ESRD (P = 0.012). In a stratified analysis according to duration of diabetes, the risk of early-onset ESRD for carriers of the Q variant was 2.3 times that for noncarriers (95% CI, 1.2-4.6). The Q variant was not associated with late-onset ESRD. Similar findings were obtained in a family-based study. We conclude that carriers of the Q variant of ENPP1 are at increased risk for developing ESRD early in the course of type 1 diabetes.

Adult↗

Phytochrome-mediated germination and early development in spores of Dryopteris filix-mas L.: phase-specific and non phase-specific inhibition by staurosporine.

The alkaloid staurosporine, currently known as the most potent inhibitor of protein kinase C, PKC, was tested for its ability to inhibit phytochrome-mediated spore germination in Dryopteris filix-mas L., evaluated by the induction of chlorophyll synthesis. Approximately half-maximal inhibition was obtained at a concentration of 10(-5) M. This effect of staurosporine was phase-specific and was found during the same period in which the presence of extracellular calcium is necessary for realization of the light signal. Furthermore, the ability of staurosporine to prevent progression of a germinated spore into early gametophyte development, evaluated by the accumulation of chlorophyll, was examined. Again, staurosporine (10(-5) M) significantly diminished chlorophyll accumulation, determined quantitatively in vivo by single-cell measurements, in a non-phase specific way. The fact that the phase-specific inhibitory effect of staurosporine in preventing germination was coincident with the phase-specific requirement of Ca2+ suggests that both Ca2+ and staurosporine affect the same step in the signal-transduction chain. A phosphorylation event catalysed by PKC or any Ca2+ -dependent protein kinase is proposed as the target of staurosporine and Ca2+.

Alkaloids↗

Two alkaline phosphatase genes are expressed during early development in the mouse embryo.

Alkaline phosphatase (AP) activity is stage specific in mouse embryos and may be associated with compaction and separation of trophectoderm from inner cell mass in preimplantation development. We previously sequenced a cDNA and two mouse AP genes that could contribute to the AP activity in embryos. Oligonucleotide primers were constructed from the three sequences and used in the reverse transcription-polymerase chain reaction technique to establish that two of the three AP isozymes are transcribed during preimplantation development. The predominant transcript (E-AP) is from a gene highly homologous to the human tissue-specific APs, but different from the mouse intestinal AP. Tissue non-specific (TN) AP also is transcribed, but there is approximately 10 times less TN-AP than E-AP transcript. The TN-AP isozyme is the predominant transcript of 7 to 14 day embryos and primordial germ cells. A switch in predominance from E-AP to TN-AP must occur during early postimplantation development. This study establishes a framework for experiments to determine the functions of the two isozymes during preimplantation development.

Alkaline Phosphatase↗

Early development and embryology of the platypus.

Information on the pre-hatching development of the platypus, Ornithorhynchus anatinus, is reliant on a small number of specimens, whose precise age is unknown. Material collected for J. P. Hill and now housed in the Hubrecht International Embryological Laboratory, Utrecht, contributes a major source of specimens. This paper presents new observations on developmental stages from the Hill collection, which allow for a more complete description of pre-hatching development. A feature of the pre-embryonic development of the platypus is the incomplete meroblastic cleavage. A column of fine yolk spheres extends from beneath the embryonic blastodisc towards the centre of a yolky vitellus, as seen in birds. The major expansion of extra-embryonic membranes occurs after the formation of the primitive streak. The primitive streak develops within an embryonal area as part of the superficial wall of the yolk-sac, a feature also shared with marsupials, birds and reptiles. The full-term, subspheroidal, intrauterine egg of the platypus has a major axis of about 17 mm and contains a flat, 19-20 somite, neurula-stage embryo which has prominent trigeminal ganglion primordia. The embryo at this stage is in a period of rapid modelling of the major early organ primordia of the nervous system, cardiovascular system, excretory system, and somite-derived components of the body wall. Soon after laying, five primary brain vesicles are present, the trigeminal ganglia CN5 as well as CN7, CN8, CN9, CN10, CN11 and CN12 are well developed. The alimentary system has an expanded stomach, pancreatic primordia and a gall bladder. Mesonephric tubules are associated with patent mesonephric ducts, which empty laterally into the cloaca. Extra-embryonic membranes at this stage show an extensive chorioamniotic connection that extends through the greater part of the caudal half of fused amniotic folds. The vascularized yolk-sac consists of a superficial yolk-sac omphalopleura and a deep yolk-sac splanchnopleure. The non-vascularized yolk-sac comprises one-quarter of the ahembryonal pole. Some distinctive monotreme features have developed by the mid-incubation period. The head is bent at an acute angle to the main body axis. The blunt upturned snout marks the site of the future oscaruncle and on the maxilla there is a median primordial papilla representing the egg tooth. The eye is open with a partly pigmented retinal ring. The forelimbs have partly separated digits, and the hindfeet are paddles. Just before hatching the upturned snout contains an oscaruncle and a sharp recurved median egg tooth. Forelimbs are pronated with separate digits possessing claw primordia. Portions of the highly vascularized extra-embryonic membranes are attached to the umbilical region and the flattened vesicular allantois has a distal region fused with the chorion. Prominent features of the hatchling are the presence of a bluntly conical oscaruncle and a translucent, horn-like egg tooth. These structures are though to enable the hatchling to extricate itself from the egg shell. At hatching, the forelimbs exhibit clawed digits and are capable of digitopalmar prehension. Hindlimbs are still paddles with digital rays. A prominent yolk-sac navel is present. The newly hatched platypus has an external form similar to that of a new-born marsupial. The early development of the platypus has many major differences to the developmental sequence for humans, which has been categorized by the use of Carnegie Stages. The rate of somitogenesis of the platypus is faster in relation to the central nervous system morphogenesis than seen in humans, and the size of the early platypus embryonal area is massive in relation to that of humans. The unique morphology and function of extra-embryonic membranes in the platypus defies comparative staging with human development. Structures adapted for altricial survival of the platypus hatchling require the acquisition of functional competence at an earlier stage of organogenesis than seen in eutherians, although they are reminiscent of those found in new-born marsupials.

Allantois↗

Early Childhood Development Programme--early detection.

The Early Childhood Development Programme has four main objectives. These are: 1. To foster child development in families with young children largely through personal involvement of the family in an education context. 2. To provide enrichment programmes to enrich the social, emotional and physical environment and to ensure that children with special needs have these needs met optimally. 3. To provide for the early detection of children who are more vulnerable because of the presence of a condition which may tend to limit optimal development and make the child more open to adverse influence of social or cultural pressures; that is a health assessment programme. 4. To provide a family support service for families of children with special needs to enable these families to foster and to fulfil themselves in the society in which they live. This family support service is seen as providing a structure for home centred parent/infant habilitation aimed at keeping the family in the main stream insofar as education and health are concerned.

Australia↗

Using the histone H2a transcript as an endogenous standard to study relative transcript abundance during bovine early development.

The requirement for sample standardization is basic to any relative RNA abundance assessment. In 2002, we published on the RNA abundance profiling of several housekeeping targets during early bovine embryonic development. It was then concluded that histone H2a was the most stable transcript across the studied developmental period. Since that time, several teams have applied this information, yet neglected to use the published set of primers. Here, we show that these other primer sets do not target the same histone H2a variant. Within the present report, the RNA abundance profiles of their respective targets, for example, histone H2a.1, H2a.z, and H2a.o were measured in developmental series spanning the immature oocyte to the blastocyst stage embryo. In order to more clearly define the conditions that impact the RNA abundance level measurement of these candidates, the state of polyadenylation and the origin of the transcript either from de novo transcription or from maternal stocks were taken into consideration. The histone H2a.z transcript is principally regulated by de novo transcription following embryonic genome activation, whereas the levels of H2a.1 and H2a.o variants are largely of maternal origin, conferring a more stable profile throughout the studied developmental window. The histone H2a.z was found solely in a polyadenylated state whereas the H2a.1 and H2a.o were found to be more abundant in a nonadenylated form. The presence of serum in the in vitro embryo production system also had some impact on the histone H2a.1 RNA level at the blastocyst stage.

Animals↗

Cell adhesion molecules in the early developing mouse retina: retinal neurons show preferential outgrowth in vitro on L1 but not N-CAM.

Both L1 and N-CAM are present on optic axons early in the developing mouse retina and optic nerve. In in vitro assays on substrates of purified cell adhesion molecules cells derived from E13 mouse retinae showed vigorous neurite extension on L1 but not on N-CAM. Although retinal neurons on N-CAM showed only limited attachment to the substrate, they were able to form lamellipodia immediately around the cell perimeter. In contrast, similarly derived cortical cells showed extensive neurite outgrowth on both substrates. Under these culture conditions, nearly all of the L1 and N-CAM present in the cell membrane appeared to be sequestered on the lower surface of the growth cones and neurites, indicating that most of these cell adhesion molecules were involved in homophilic interactions. Our results suggest differential roles for L1 and N-CAM in initiation and establishment of the optic pathway.

Animals↗

The armadillo homologs beta-catenin and plakoglobin are differentially expressed during early development of Xenopus laevis.

Plakoglobin and beta-catenin are cytoplasmic proteins associated with the intracellular plaques of cell adhesive junctions. While plakoglobin is present in both adherens junctions and desmosomes, beta-catenin is associated with the cadherins that accumulate only in adherens junctions. Both beta-catenin and plakoglobin are homologs of armadillo, a Drosophila segment polarity gene that is considered to be in the wingless signaling pathway. We have characterized the expression and distribution of both plakoglobin and beta-catenin in Xenopus embryos. As shown by RNA blot analysis, beta-catenin and plakoglobin transcripts are present in fertilized eggs and in embryos through to tadpole stage. Whole-mount in situ hybridization indicates that both genes are expressed in the dorsal ectoderm and mesoderm of tailbud- and tadpole-stage embryos and that beta-catenin is expressed in the midbrain. Both plakoglobin and beta-catenin polypeptides are present during early Xenopus development; however, differences exist in the timing of maximal expression. Plakoglobin is present in the fertilized egg, increases in abundance by neurula stage, then declines at the tailbud and tadpole stages. beta-Catenin, recognized by an anti-arm antibody, is also present in the fertilized egg and in blastula-stage embryos. However, beta-catenin continues to be detected at the neurula, tailbud, and tadpole stages when levels of plakoglobin decline. The presence of multiple homologs of armadillo in Xenopus embryos and the differences in their patterns of expression suggest distinct roles for these proteins in processes affected by cell adhesion.

Amino Acid Sequence↗

Expression of the nicotinic receptor alpha 7 gene in tendon and periosteum during early development.

One of the most abundant nicotinic acetylcholine receptors expressed in the central and peripheral nervous systems is a species that contains the alpha 7 gene product, binds alpha-bungarotoxin with high affinity, and has a high relative permeability to calcium. The alpha 7 gene is also expressed at low levels in embryonic muscle tissue. We show here that the alpha 7 gene is expressed in tendon fibroblasts and periosteal cells during development. In situ hybridizations identify alpha 7 transcripts in tissue sections containing embryonic tendon and periosteum. RNase protection experiments demonstrate alpha 7 mRNA in primary tendon cells grown in culture. Immunofluorescence with subunit-specific monoclonal antibodies reveals alpha 7 protein in embryonic tendon. Immunoprecipitation assays with the antibodies indicate that the alpha 7-containing species in tendon is capable of binding alpha-bungarotoxin and that a similar species can be identified at low levels on the surface of fibroblasts in culture. The results show that the alpha 7 gene product is expressed in a range of tissues, including cells thought to be nonexcitable. The distribution of alpha 7 expression early in development and the ability of alpha 7-containing receptors to elevate intracellular calcium suggest that the gene may influence a variety of calcium-dependent events during embryogenesis.

Animals↗

An essential role for functional telomeres in mouse germ cells during fertilization and early development.

Late generations of telomerase-null (TR(-/-)) mice exhibit progressive defects in highly proliferative tissues and organs and decreased fertility, ultimately leading to sterility. To determine effects of telomerase deficiency on germ cells, we investigated the cleavage and preimplantation development of embryos derived from both in vivo and in vitro fertilization of TR(-/-) or wild-type (TR(+/+)) sperm with either TR(-/-) or TR(+/+) oocytes. Consistently, fertilization of TR(-/-) oocytes with either TR(+/+) or TR(-/-) sperm, and TR(-/-) sperm with TR(+/+) oocytes, resulted in aberrant cleavage and development, in contrast to the normal cleavage and development of TR(+/+) oocytes fertilized by TR(+/+) sperm. Many (>50%) of the fertilized TR(-/-) eggs developed only one pronucleus, coincident with increased incidence of cytofragmentation, in contrast to the normal formation of two pronuclei and equal cleavage of wild-type embryos. These results suggest that both TR(-/-) sperm and oocytes contribute to defective fertilization and cleavage. We further found that a subset (7-9%) of telomeres was undetectable at the ends of some metaphase I chromosomes from TR(-/-) spermatocytes and oocytes, indicating that meiotic germ cells lacking telomerase ultimately resulted in telomere shortening and loss. Dysfunction of meiotic telomeres may contribute to aberrant fertilization of gametes and lead to abnormal cleavage of embryos, implying an important role of functional telomeres for germ cells undergoing fertilization and early cleavage development.

Animals↗

Formation and early development of follicles in the polycystic ovary.

BACKGROUND: Polycystic ovary syndrome is the most common cause of anovulatory infertility. It has long-term health implications and is an important risk factor for type 2 diabetes. However, little is known about the cause of polycystic ovaries. We have used detailed morphological analysis to assess the hypothesis that there is an intrinsic ovarian abnormality that affects the earliest stages of follicular development. METHODS: We took small cortical biopsies during routine laparoscopy from 24 women with normal ovaries and regular cycles and from 32 women with polycystic ovaries, 16 of whom had regular, ovulatory cycles and 16 of whom had oligomenorrhoea. We used computerised image analysis to assess the density and developmental stage of small preantral follicles in serial sections of fixed tissue. FINDINGS: Median density of small preantral follicles, including those at primordial and primary stages, was six-fold greater in biopsies from polycystic ovaries in anovulatory women than in normal ovaries (p=0.009). In both ovulatory and anovulatory women with polycystic ovaries, we noted a significant increase in the percentage of early growing (primary) follicles and a reciprocal decrease in the proportion of primordial follicles compared with normal ovaries. INTERPRETATION: Our findings indicate that there are fundamental differences between polycystic and normal ovaries in early follicular development, suggesting an intrinsic ovarian abnormality. The increased density of small preantral follicles in polycystic ovaries could result from increased population of the fetal ovary by germ cells, or from decreased rate of loss of oocytes during late gestation, childhood, and puberty.

Adult↗