We have published three papers which made use of Ingeneue have others in review. 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.

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.

We believe in encouraging scientific correspondence, especially correspondence that may point out weaknesses in our work. To that end, here is a letter from Drs. Cadigan and Grossniklaus which was originally submitted to Nature as a critical comment on our paper on the segment polarity network. Nature declined to print it, which is unfortunate because a) the authors are basically right, b) Nature is one of the only journals that retains even the pretense of a printed forum for discussion of papers after their publication, and c) this is exactly the kind of feedback that helps us improve our models. So therefore we decided, with Dr. Cadigan's permission, to post the letter here.

The first tutorial that comes with the program download 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.

There is a supplement to this Current Biology paper available here.

Files to reproduce the results in this paper are here.

Ingeneue: a versatile tool for reconstituting genetic networks in silico.

Meir, E., G. von Dassow, E. Munro, G. M. Odell. J. Experimental Zoology, in press.

< Abstract will appear after paper is published>