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N A Monk

Publications and source records attributed to N A Monk.

10 recordsLinked to original sources
PubMed1998

Restricted-range gradients and travelling fronts in a model of juxtacrine cell relay.

Patterning events in development often depend on the transmission over a range of several cell diameters of signals emanating from a localized source. Experimental studies of such long-range signalling by members of the TGF-beta family of growth factors suggests that a cell-relay mechanism in which cells signal only with their immediate neighbours (i.e., juxtacrine signalling) may be operating in some tissues. Here, this possibility is investigated through the analysis of a model of juxtacrine signalling. Depending on the strength of the signal relay between cells, a localized signal source can generate either stable gradients or travelling fronts of cell activation. Both of these behaviors could in principle be involved in the long-range transmission of signals and patterning of cell fates by cell relays. There are significant and surprising differences between the gradients generated by the mechanism studied here, and those generated by the diffusion of a morphogen. In particular, there is an upper limit on the distance over which any given level of cell activation can be attained in a relay-mediated gradient. irrespective of the strength of signal source.

Animals↗
PubMed1997

The community effect and ectoderm-mesoderm interaction in Xenopus muscle differentiation.

Community effects are believed to play an important role in the patterning of many tissues during development. They involve an interaction between neighbouring equivalent cells that is necessary for them to proceed to their fully differentiated state. However, the mechanisms underlying these effects remain unclear. In this paper, diffusion-based mathematical models are constructed and analysed in order to study possible mechanisms for the community effect in Xenopus muscle differentiation. These models differ from each other in the assumptions that are made about the nature of an inhibitory effect that ectodermal tissue has been observed to have on muscle differentiation. It is possible to construct consistent models based on all the forms of inhibition considered. However, each model requires the diffusible factors on which it is based to have different properties. The current data from tissues reaggregate experiments are insufficient to determine the mechanisms underlying the community effect; the work presented here suggests that quantitative analysis of a further series of reaggregate experiments will make it possible to distinguish between the proposed mechanisms.

Animals↗
PubMed1997

Cell communities and robustness in development.

The robustness of patterning events in development is a key feature that must be accounted for in proposed models of these events. When considering explicitly cellular systems, robustness can be exhibited at different levels of organization. Consideration of two widespread patterning mechanisms suggests that robustness at the level of cell communities can result from variable development at the level of individual cells; models of these mechanisms show how interactions between participating cells guarantee community-level robustness. Cooperative interactions enhance homogeneity within communities of like cells and the sharpness of boundaries between communities of distinct cells, while competitive interactions amplify small inhomogeneities within communities of initially equivalent cells, resulting in fine-grained patterns of cell specialization.

Animals↗
PubMed1996

Pattern formation by lateral inhibition with feedback: a mathematical model of delta-notch intercellular signalling.

In many developing tissues, adjacent cells diverge in character so as to create a fine-grained pattern of cells in contrasting states of differentiation. It has been proposed that such patterns can be generated through lateral inhibition--a type of cell-cell interaction whereby a cell that adopts a particular fate inhibits its immediate neighbors from doing likewise. Lateral inhibition is well documented in flies, worms and vertebrates. In all of these organisms, the transmembrane proteins Notch and Delta (or their homologues) have been identified as mediators of the interaction--Notch as receptor, Delta as its ligand on adjacent cells. However, it is not clear under precisely what conditions the Delta-Notch mechanism of lateral inhibition can generate the observed types of pattern, or indeed whether this mechanism is capable of generating such patterns by itself. Here we construct and analyse a simple and general mathematical model of such contact-mediated lateral inhibition. In accordance with experimental data, the model postulates that receipt of inhibition (i.e. activation of Notch) diminished the ability to deliver inhibition (i.e. to produce active Delta). This gives rise to a feedback loop that can amplify differences between adjacent cells. We investigate the pattern-forming potential and temporal behaviour of this model both analytically and through numerical simulation. Inhomogeneities are self-amplifying and develop without need of any other machinery, provided the feedback is sufficiently strong. For a wide range of initial and boundary conditions, the model generates fine-grained patterns similar to those observed in living systems.

Animals↗
PubMed1991

The phenotype in placental trisomy 7.

Trisomy 7, in mosaic state, was identified at chorionic villus sampling. The pregnancy was closely followed, and proceeded uneventfully. Mosaic trisomy 7 was confirmed in the term placenta, the organ having no structural abnormalities; the karyotype of the phenotypically normal baby was 46,XY. Trisomy 7, mosaic or nonmosaic, detected at chorionic villus sampling in an ultrasonographically normal pregnancy, appears typically to be associated with a normal fetal karyotype, and placental growth, structure, and function are not discernibly compromised.

Adult↗
PubMed1990

Early prenatal diagnosis of genetic abnormality by chorion villus sampling.

We describe a series of 100 cases of prenatal genetic diagnosis using the technique of chorion villus sampling. The advantage of chorion villus sampling in terms of earlier diagnosis, and its disadvantage of a higher incidence of false results, compared with amniocentesis, are noted. The comparative risks for pregnancy loss are discussed.

Abortion, Spontaneous↗
PubMed1989

Trisomy 16 detected at chorion villus sampling.

Trisomy 16 detected at chorion villus sampling (CVS) may reflect the placental but not the fetal karyotype. We describe a case in which the pregnancy continued until intrauterine death at 37 weeks. Cytogenetic study of two placental samples showed 47, + 16 and 46,XX; the fetus was morphologically grossly normal, but fetal tissue culture was unsuccessful. Conservative management may be appropriate when trisomy 16 is detected at CVS and the pregnancy is normal ultrasonographically.

Adult↗
PubMed1986

Ring 21 chromosome: the mild end of the phenotypic spectrum.

The case is reported of a child with the karyotype 46,XY,r(21), who presented with linear growth retardation but who appears, at age 2 years 8 months, to be developing normally mentally. There is a small number of reports of mildly affected cases of r(21), and of some with an apparently completely normal phenotype. We presume a structural and functional cytogenetic heterogeneity underlies the observed phenotypic heterogeneity in the ring 21 spectrum.

Child, Preschool↗