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Biomedical subjects

U K Abbott

Publications and source records attributed to U K Abbott.

At least 19 recordsLinked to original sources
PubMed1998

An avian model for comparative studies of insulin teratogenicity.

This study was designed to explore the effects of purified insulin during early stages of chick embryo development, and to search for variations between different molecular structures of the hormone. Chicken embryos were treated in ovo with a single dose of insulin (porcine or bovine), in only one stage of development between day 0 and day 9. Two susceptible periods were found. The earliest period (day 0 to day 3), characterized by abnormalities in the caudal vertebrae and a high mortality rate, was followed by a period with a different set of malformations, a syndrome classified as achondroplasia. The rate of achondroplastic embryos was significantly higher with porcine rather than with bovine insulin. Paradoxically, insulin at physiological doses has stimulatory effects in growth and development but, in contrast, has inhibitory effects at higher doses. The precise signalling cascade of events in the target cells is still unclear. The possible interpretations of our results are discussed. The similarity between the insulin-induced abnormalities in the chicken embryos and the caudal regression syndrome, the most common malformation found in infants of diabetic women, suggests a common mechanism. This circumstance offers the chicken embryos as an excellent in vivo model for research on the mechanism of action of insulin during normal and abnormal development.

Abnormalities, Drug-Induced↗
PubMed1997

Expression of Radical fringe in limb-bud ectoderm regulates apical ectodermal ridge formation.

The apical ectodermal ridge of the vertebrate limb bud lies at the junction of the dorsal and ventral ectoderm and directs patterning of the growing limb. Its formation is directed by the boundary between cells that do and cells that do not express the gene Radical fringe. This is similar to the establishment of the margin cells at the Drosophila wing dorsoventral border by fringe. Radical fringe expression in chick-limb dorsal ectoderm is established in part through repression by Engrailed-1 in the ventral ectoderm.

Animals↗
PubMed1996

Shh, HoxD, Bmp-2, and Fgf-4 gene expression during development of the polydactylous talpid2, diplopodia1, and diplopodia4 mutant chick limb buds.

Several polydactylous mutants affect the pattern of asymmetry along the anteroposterior axis of the vertebrate limb. In talpid2, diplopodia1, and diplopodia4 chick limb mutants, there is a preaxial extension that results in broader limb buds. Talpid2 shows reduction of the long bones and 9-10 syndactylous digits, none of which are specifically recognizable as members of the normal digit complement. In diplopodia1 and diplopodia4 extra digits are present preaxially in addition to the normal digits. This phenotype resembles the duplications obtained by grafting a polarizing region to the anterior margin of the limb bud. The abnormal skeletal pattern along the anteroposterior limb axis in both mutants suggests alterations in the signaling pathways that mediate growth and patterning of the limb. In situ hybridization studies reveal that whereas shh transcripts are restricted to the posterior limb margins, HoxD, Bmp-2, and Fgf-4 genes are ectopically expressed in the anterior region of the talpid2, diplopodia1, and diplopodia4 limb buds. The results obtained give insights into the molecular basis of talpid2 and diplopodia mutations and also into the possible roles of shh, Bmp-2, HoxD, and Fgf-4 genes in vertebrate limb morphogenesis.

Animals↗
PubMed1996

The chick limbless mutation causes abnormalities in limb bud dorsal-ventral patterning: implications for the mechanism of apical ridge formation.

In chick embryos homozygous for the limbless mutation, limb bud outgrowth is initiated, but a morphologically distinct apical ridge does not develop and limbs do not form. Here we report the results of an analysis of gene expression in limbless mutant limb buds. Fgf4, Fgf8, Bmp2 and Msx2, genes that are expressed in the apical ridge of normal limb buds, are not expressed in the mutant limb bud ectoderm, providing molecular support for the hypothesis that limb development fails in the limbless embryo because of the inability of the ectoderm to form a functional ridge. Moreover, Fgf8 expression is not detected in the ectoderm of the prospective limb territory or the early limb bud of limbless embryos. Since the early stages of limb bud outgrowth occur normally in the mutant embryos, this indicates that FGF8 is not required to promote initial limb bud outgrowth. In the absence of FGF8, Shh is also not expressed in the mutant limb buds, although its expression can be induced by application of FGF8-soaked beads. These observations support the hypothesis that Fgf8 is required for the induction of Shh expression during normal limb development. Bmp2 expression was also not detected in mutant limb mesoderm, consistent with the hypothesis that SHH induces its expression. In contrast, SHH is not required for the induction of Hoxd11 or Hoxd13 expression, since expression of both these genes was detected in the mutant limb buds. Thus, some aspects of mesoderm A-P patterning can occur in the absence of SHH and factors normally expressed in the apical ridge. Intriguingly, mutant limbs rescued by local application of FGF displayed a dorsalized feather pattern. Furthermore, the expression of Wnt7a, Lmx1 and En1, genes involved in limb D-V patterning, was found to be abnormal in mutant limb buds. These data suggest that D-V patterning and apical ridge formation are linked, since they show that the limbless mutation affects both processes. We present a model that explains the potential link between D-V positional information and apical ridge formation, and discuss the possible function of the limbless gene in terms of this model.

Animals↗
PubMed1993

Making the connection: exploring classical concepts in normal and abnormal limb development using contemporary approaches.

Classical studies of the vertebrate limb have provided a firm foundation for recent investigations into the molecular control of mechanisms governing limb patterning. The early studies revealed the importance of inductive tissue interactions in developing systems, the spatiotemporal restrictions of these interactions, and the conservation of inductive signals between different tissues and even different species. They incorporated a number of different experimental approaches, including: homologous and heterologous tissue grafting and recombination, the investigation of several limb mutations, and examination of the response of normal limb tissue to a variety of teratogenic treatments. While some of the mutations studied only affected the limbs, most were highly pleiotropic, producing complex syndromes that altered the development of several embryonic structures in addition to the limbs. Some of these syndromes could be partially or completely phenocopied (mimicked) by specific chemical or physical treatments. One such gene-phenocopy pairing that we have studied is that of the mutation wingless-2 and the syndrome produced by treatment with retinoic acid. Another aspect of abnormal pattern formation we explored is the interaction between wingless-2 and eudiplopodia.

Animals↗
PubMed1989

Distribution of extracellular matrix in the migratory pathway of avian primordial germ cells.

The appearance and distribution of extracellular matrix (ECM) was documented along the migratory route of chicken primordial germ cells (PGCs). The antimouse embryonal carcinoma cell antibody, EMA-1, was used to label PGCs (Urven et al.: Development 103:299-304, 1988). Antibodies against laminin, fibronectin, chondroitin sulfate proteoglycan and collagen type IV were used to label extracellular matrix components. When the PGCs emerged from the epiblast, all four ECM molecules were restricted principally to the basement membrane of the epiblast. Chondroitin sulfate was also located between hypoblast cells during this period. In late germinal crescent stages, when the PGCs entered the lumina of blood vessels, the same ECM molecules were more widespread in the mesoderm and in extracellular spaces. In addition, laminin and collagen type IV were identified on lateral surfaces of ectodermal cells at this stage. When the germ cells moved through the mesenchyme into the germinal ridge, the ECM molecules were found around mesenchymal cells, and, in the cases of laminin, fibronectin and collagen type IV, in the basement membranes of the germinal ridge epithelia. Because the appearance of these ECM components is temporally and spatially correlated with the movement of PGCs, we suggest that early PGC migration may depend on their timely appearance.

Animals↗
PubMed1988

Analysis of germ line development in the chick embryo using an anti-mouse EC cell antibody.

We have found that EMA-1, a monoclonal antibody originally raised against mouse embryonal carcinoma (Nulli SCC1) cells (Hahnel & Eddy, 1982), also labels chick primordial germ cells (PGCs). We have used this antibody in immunohistological studies to follow the development of PGCs in the chick embryo from the time of their initial appearance beneath the epiblast, through their migratory phase and subsequent colonization of the germinal epithelium. During hypoblast formation, individual EMA-1-labelled cells appeared to separate from the basal surface of the epiblast and enter the blastocoel, coincident with the appearance of morphologically identifiable PGCs in this same area. EMA-1 continued to label germ cells until the initiation of gametogenesis in each sex; specifically, labelling was absent by 7-8 days of incubation in females and started to decrease at 11 days of incubation in males. There was a recurrence of the epitope on oogonia at 15 days of incubation, but not on spermatogonia during the remainder of development through hatching. These observations are consistent with an epiblast origin for the avian germ line, and are strikingly similar to those reported for the early mouse embryo using the same antibody (Hahnel & Eddy, 1986).

Animals↗
PubMed1984

Tissue densities in developing avian embryos.

Changes in the weight:mass ratio provide the physical basis for the biological responses of terrestrial organisms to alteration in the ambient acceleration field. Where organisms such as aquatic animals occupy dense media, changes in the gravitational environment produce compensating changes in the weight:mass ratios of organism and medium, such that little net load is imposed upon the organism. This relationship also applies to organs of terrestrial animals. Changes in the ambient acceleration field produce compensatory changes in surrounding tissues so that the organ may not develop a significant net load. This relationship has been investigated in the case of the vertebrate brain. However, density gradients within the organ/organism will produce a local gravitational loading, which may lead to biological responses. In fact, a significant density gradient would be an essential character for a gravity receptor. Prenatal development, both in mammals and birds, occurs characteristically in a buoyant condition. In both cases a volume of amniotic fluid develops and surrounds the embryo while it is still of microscopic size. This situation prevails until the latest stages of prenatal development. In mammals the amniotic fluid is lost immediately prior to parturition through rupture of the sac. In chick embryos the amniotic fluid is ingested, beginning on the 13th day with the process being completed by the 18th day of development, just prior to the pre-hatch reorientation of the embryo. Consequently, a net load upon the embryo/fetus is not considered to be a major factor in gravitational experiments of prenatal development. Prenatal development includes marked changes in chemical composition as well as changes in size. This is readily apparent from extensive and detailed examination of the chemical growth for the chick embryo. These chemical materials vary in density, as well as in distribution among the tissues of the developing organism. Consequently, the existence of density gradients, and changes in them may be anticipated during prenatal development.

Albumins↗
PubMed1979

Adult and embryo responses to organophosphate pesticides: azodrin.

Azodrin was applied to adult embryo chickens, Chukar Partridge, and Bobwhite Quail. Chronic exposure of adult birds to Azodrin mixed in their feed indicated that no a priori predictions could be made about one species based on the results of another; each had a different no effect (MACT) level. The chickens were between 25 and 100 ppm, the Chukar Partridge 5 and 25 ppm, and the Bobwhite quail less than 1.25 ppm. The chicken adults were most resistant, and the quail were least resistant to chronic exposure to Azodrin. Yolk-injected Azodrin caused the embryos of all three species to develop abnormally. The chicken and Chukar embryos developed a generalized achondroplasia, the quail were amuscular, only. In general, the 3 day quail embryos were most resistant to injected Azodrin and the chicken embryo least resistant. The relationship between adult and embryo response was negative.

Animals↗
PubMed1978

Facial development in normal and mutant chick embryos. I. Scanning electron microscopy of primary palate formation.

Early facial development in normal chick embryos was studied by scanning electron microscopy, and compared to the abnormal facial development of a mutant in which primary palate formation does not occur, thus resulting in bilateral cleft lip. In both normal and "cleft primary palate" mutant embryos, subsequent to the appearance of the nasal placodes, the surrounding tissues elevate to give rise to the presumptive facial primordia. As the facial primordia grow forward, they gradually assume the configuration of a square which is most pronounced at five days development. In normal embryos, the square configuration is then lost as the facial primordia become aligned in preparation for primary palate formation. The primary palate is formed at six days development by fusion of the "free-ended" medial nasal processes with the combined lateral nasal and maxillary processes across the nasal grooves. Just prior to fusion, long, slender filaments extend from the apposing surfaces of the facial primordia in the regions of prefusion contact. It is speculated that these "prefusion filaments" may function in alignment or adhesion of the facial primordia. In "cleft primary palate" embryos, facial morphogenesis appears to arrest at five days development, so that the square configuration persists. The medial nasal processes never contact the lateral nasal and maxillary processes, but instead remain separated from them by wide nasal grooves. Furthermore, facial primordia of mutant embryos do not exhibit the "prefusion filaments" characteristic of normal embryos.

Animals↗
PubMed1977

Temporal, morphological, and genetic responses of avian embryos to Azodrin, an organophosphate insecticide.

The effect of Azodrin on avian development was studied using a bobwhite quail line and two chicken lines--a single comb White Leghorn (SCWL) and an Australorp line. The bobwhite quail embryos did not respond to injections of Azodrin until stages 22 to 23 (6 days of incubation); the SCWL embryos, not until stage 18 (3 days of incubation) with increasing susceptibility through stage 20. The threshold concentration, at stage 19, for the SCWL was 0.4 mg/kg, for the Australorp, less. Within one hour of treatment stage-20 embryo shape was altered. There was, however, no immediate response from embryos treated earlier. The effect appeared as a reduced growth rate in the cervical flexure, and may be mediated by interference with the normal energy balance. The response, once initiated, was continuous through 10 days of incubation.

Abnormalities, Drug-Induced↗