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Morphogen gradients, which provide positional information to cells in a developing tissue, could in principle adopt any nonuniform profile. To our knowledge, how the profile of a morphogen gradient affects positional precision has not been well studied experimentally. Here, we compare the positional precision provided by the Drosophila morphogenetic protein Bicoid (Bcd) in wild-type (wt) embryos with embryos lacking an interacting cofactor. The Bcd gradient in the latter case exhibits decreased positional precision around mid-embryo compared with its wt counterpart. The domain boundary of Hunchback (Hb), a target activated by Bcd, becomes more variable in mutant embryos. By considering embryo-to-embryo, internal, and measurement fluctuations, we dissect mathematically the relevant sources of fluctuations that contribute to the error in positional information. Using this approach, we show that the defect in Hb boundary positioning in mutant embryos is directly reflective of an altered Bcd gradient profile with increasing flatness toward mid-embryo. Furthermore, we find that noise in the Bcd input signal is dominated by internal fluctuations but, due to time and spatial averaging, the spatial precision of the Hb boundary is primarily affected by embryo-to-embryo variations. Our results demonstrate that the positional information provided by the wt Bcd gradient profile is highly precise and necessary for patterning precision.

We study the effect in geometrically frustrated antiferromagnets of weak, random variations in the strength of exchange interactions. Without disorder the simplest classical models for these systems have macroscopically degenerate ground states, and this degeneracy may prevent ordering at any temperature. Weak exchange randomness favours a small subset of these ground states and induces a spin-glass transition at an ordering temperature determined by the amplitude of modulations in interaction strength. We use the replica approach to formulate a theory for this transition, showing that it falls into the same universality class as conventional spin-glass transitions. In addition, we show that a model with a low concentration of defect bonds can be mapped onto a system of randomly located pseudospins that have dipolar effective interactions. We also present detailed results from Monte Carlo simulations of the classical Heisenberg antiferromagnet on the pyrochlore lattice with weak randomness in nearest neighbour exchange., 10 pages. Published version.

During development, morphogen gradients precisely determine the position of gene expression boundaries despite the inevitable presence of fluctuations. Recent experiments suggest that some morphogen gradients may be interpreted prior to reaching steady-state. Theoretical work has predicted that such systems will be more robust to embryo-to-embryo fluctuations. By analysing two experimentally motivated models of morphogen gradient formation, we investigate the positional precision of gene expression boundaries determined by pre-steady-state morphogen gradients in the presence of embryo-to-embryo fluctuations, internal biochemical noise and variations in the timing of morphogen measurement. Morphogens that are direct transcription factors are found to be particularly sensitive to internal noise when interpreted prior to steady-state, disadvantaging early measurement, even in the presence of large embryo-to-embryo fluctuations. Morphogens interpreted by cell-surface receptors can be measured prior to steady-state without significant decrease in positional precision provided fluctuations in the timing of measurement are small. Applying our results to experiment, we predict that Bicoid, a transcription factor morphogen in Drosophila, is unlikely to be interpreted prior to reaching steady-state. We also predict that Activin in Xenopus and Nodal in zebrafish, morphogens interpreted by cell-surface receptors, can be decoded in pre-steady-state., Comment: 18 pages, 3 figures

Morphogen profiles play a vital role in biology by specifying position in embryonic development. However, the factors that influence the shape of a morphogen profile remain poorly understood. Since morphogens should provide precise positional information, one significant factor is the robustness of the profile to noise. We compare three classes of morphogen profiles (linear, exponential, algebraic) to see which is most precise when subject to both external embryo-to-embryo fluctuations and internal fluctuations due to intrinsically random processes such as diffusion. We find that both the kinetic parameters and the overall gradient shape (e.g. exponential versus algebraic) can be optimised to generate maximally precise positional information., Comment: 5 pages, 3 figures

We study geometrically frustrated antiferromagnets with magnetoelastic coupling. Frustration in these systems may be relieved by a structural transition to a low temperature phase with reduced lattice symmetry. We examine the statistical mechanics of this transition and the effects on it of quenched disorder, using Monte Carlo simulations of the classical Heisenberg model on the pyrochlore lattice with coupling to uniform lattice distortions. The model has a transition between a cubic, paramagnetic high-temperature phase and a tetragonal, Neel ordered low-temperature phase. It does not support the spin-Peierls phase, which is predicted as an additional possibility within Landau theory, and the transition is first-order for reasons unconnected with the symmetry analysis of Landau theory. Quenched disorder stabilises the cubic phase, and we find a phase diagram as a function of temperature and disorder strength similar to that observed in ZnCdCrO., 8 pages, 8 figures

Many classical, geometrically frustrated antiferromagnets have macroscopically degenerate ground states. In a class of three-dimensional systems, the set of degenerate ground states has power-law correlations and is an example of a Coulomb phase. We investigate Neel ordering from such a Coulomb phase, induced by weak additional interactions that lift the degeneracy. We show that the critical point belongs to a universality class that is different from the one for the equivalent transition out of the paramagnetic phase, and that it is characterised by effective long-range interactions; alternatively, ordering may be discontinuous. We suggest that a transition of this type may be realised by applying uniaxial stress to a pyrochlore antiferromagnet., Comment: 4 pages, 3 figures

During development, multicellular organisms must accurately control both temporal and spatial aspects of tissue patterning. This is often achieved using morphogens, signaling molecules that form spatially varying concentrations and so encode positional information. Typical analysis of morphogens assumes that spatial information is decoded in steady state by measuring the value of the morphogen concentration. However, recent experimental work suggests that both pre-steady-state readout and measurement of spatial and temporal derivatives of the morphogen concentration can play important roles in defining boundaries. Here, we undertake a detailed theoretical and numerical study of the accuracy of patterning—both in space and time—in models where readout is provided not by the morphogen concentration but by its spatial and temporal derivatives. In both cases we find that accurate patterning can be achieved, with sometimes even smaller errors than directly reading the morphogen concentration. We further demonstrate that such models provide other potential benefits to the system, such as the ability to switch on and off gene response with a high degree of spatiotemporal accuracy. Finally, we discuss how such derivatives might be calculated biologically and examine these models in relation to Sonic Hedgehog signaling in the vertebrate central nervous system. We show that, when coupled to a downstream transcriptional network, pre-steady-state measurement of the temporal change in the Shh morphogen is a plausible mechanism for determining precise gene boundaries in both space and time.