Papers Using Ingeneue

We have published four papers which made use of Ingeneue have others in preparation. We list references and abstracts here. We would also be delighted to put up references to anyone else's paper that makes use of Ingeneue - just email us. If you publish a paper using Ingeneue, you should reference one of the papers below.

For a list of publications by members of the Center for Cell Dynamics, follow this link.

The segment polarity network is a robust developmental module.

von Dassow, G, E. Meir, E Munro, G. M. Odell. 2000. Nature 406: 188-92.

There is a supplement to this Nature paper available here.

Abstract: All insects possess homologous segments, but segment specification differs radically among insect orders. In Drosophila maternal morphogens control patterned activation of gap genes, which encode transcriptional regulators that shape patterned expression of pair-rule genes. This patterning cascade takes place before cellularization. Pair-rule gene products subsequently "imprint" segment polarity genes with reiterated patterns, thus defining the primordial segments. This mechanism must be drastically modified in various insect groups in which many segments emerge only after cellularization. In beetles and parasitic wasps pair-rule homologues are expressed in patterns consistent with roles during segmentation, but these patterns emerge within cellular fields. Locust pair-rule homologues may not control segmentation. However, at least some segment polarity genes and their interactions are conserved. Perhaps segmentation is modular, each module autonomously expressing a characteristic intrinsic behavior in response to transient stimuli. If so, evolution could rearrange inputs to modules without changing their intrinsic behaviors. Here we suggest, using computer simulations, that the Drosophila segment polarity genes constitute such a module, and that this module is robust to varying kinetic constants governing its behavior.

The first tutorial that comes with Ingeneue essentially shows you how to recreate the results in this paper.

Robustness, flexibility, and the role of lateral inhibition in the neurogenic network.

Meir, E., G. von Dassow, E. Munro, G. M. Odell. 2002. Current Biology, 12:778-786

Abstract: Background: Many gene networks used by developing organisms have been conserved over long periods of evolutionary time. Why is that? We showed previously that a model of the segment polarity network in Drosophila is robust to parameter variation and is likely to act as a semi-autonomous patterning module. Is this true of other networks as well?
Results: We present a model of the core neurogenic network in Drosophila. Our model exhibits at least three related pattern-resolving behaviors that the real neurogenic network accomplishes during embryogenesis in Drosophila. Furthermore, we find that it exhibits these behaviors across a wide range of parameter values, with most of its parameters able to vary more than an order of magnitude while it still successfully forms our test patterns. With a single set of parameters, different initial conditions (pre-patterns) can select between different behaviors in the network's repertoire. We introduce two new measures for quantifying network robustness that mimic recombination and allelic divergence, and use these to reveal the shape of the domain in parameter space in which the model functions. We show lateral inhibition yields robustness to changes in pre-pattern, and suggest a reconciliation of two divergent sets of experimental results. Finally, we show that, for this model, robustness confers functional flexibility.
Conclusions: The neurogenic network is robust to changes in parameter values, which gives it the flexibility to make new patterns. Our model also offers a possible resolution of a debate on the role of lateral inhibition in cell fate specification.

Ingeneue: a versatile tool for reconstituting genetic networks, with examples from the segment polarity network

Meir, E., G. von Dassow, E. Munro, G. M. Odell. 2002. J. Experimental Zoology, 294: 216-251

Abstract: Here we describe a software tool for synthesizing molecular genetic data into models of genetic networks. Our software program Ingeneue, written in Java, lets the user quickly turn a map of a genetic network into a dynamical model consisting of a set of ordinary differential equations. We developed Ingeneue as part of an ongoing effort to explore the design and evolvability of genetic networks. Ingeneue has three principal advantages over other available mathematical software: it automates instantiation of the same network model in each cell in a 2-D sheet of cells; it constructs model equations from pre-made building blocks corresponding to common biochemical processes; and it automates searches through parameter space, sensitivity analyses, and other common tasks. Here we discuss the structure of the software and some of the issues we have dealt with. We conclude with some examples of results we have achieved with Ingeneue for the Drosophila segment polarity network.

Design and constraints of the Drosophila segment polarity module: robust spatial patterning emerges from intertwined cell state switches

G. von Dassow and G. M. Odell. 2002. J. Experimental Zoology, 294: 179-215

Abstract: The Drosophila segment polarity genes constitute the last tier in the segmentation cascade; their job is to maintain the boundaries between parasegments and provide positional "read-outs" within each parasegment for the entire developmental history of the animal. These genes constitute a relatively well-defined network with a relatively well-understood patterning task. In a previous publication (von Dassow et al. 2000. Nature 406:188-192) we showed that a computer model predicts the segment polarity network to be a robust boundary-making device. Here we elaborate those findings. First, we explore the constraints among parameters that govern the network model. Second, we test architectural variants of the core network, and show that the network tolerates a wide variety of adjustments in design. Third, we evaluate several topologically identical models that incorporate more or less molecular detail, finding that more-complex models perform noticeably better than simplified ones. Fourth, we discuss two instances in which the failure of the network model to behave in a life-like fashion highlights mechanistic details that need further experimental investigation. We conclude with an explanation of how the segment polarity network can be understood as an interwoven conspiracy of simple dynamical elements, several bistable switches and a homeostat. The robustness with which the network as a whole maintains a spatial regime of stable cell state emerges from generic dynamical properties of these simple elements.