Trainable Gene Regulation Networks with Applications to Drosophila Pattern Formation

This chapter will very briefly introduce and review some computational experiments in using trainable gene regulation network models to simulate and understand selected episodes in the development of the fruit fly, Drosophila melanogaster. For details the reader is referred to the papers introduced below. It will then introduce a new gene regulation network model which can describe promoter-level substructure in gene regulation. As described in chapter 2, gene regulation may be thought of as a combination of cis-acting regulation by the extended promoter of a gene (including all regulatory sequences) by way of the transcription complex, and of trans-acting regulation by the transcription factor products of other genes. If we simplify the cis-action by using a phenomenological model which can be tuned to data, such as a unit or other small portion of an artificial neural network, then the full transacting interaction between multiple genes during development can be modelled as a larger network which can again be tuned or trained to data. The larger network will in general need to have recurrent (feedback) connections since at least some real gene regulation networks do. This is the basic modeling approach taken, which describes how a set of recurrent neural networks can be used as a modeling language for multiple developmental processes including gene regulation within a single cell, cell-cell communication, and cell division. Such network models have been called "gene circuits", "gene regulation networks", or "genetic regulatory networks", sometimes without distinguishing the models from the actual modeled systems.

[1]  H. Jäckle,et al.  Krüppel requirement for knirps enhancement reflects overlapping gap gene activities in the Drosophila embryo , 1989, Nature.

[2]  C. Nüsslein-Volhard,et al.  A gradient of bicoid protein in Drosophila embryos , 1988, Cell.

[3]  P. Lawrence The making of a fly , 1992 .

[4]  M. Levine,et al.  Regulation of even‐skipped stripe 2 in the Drosophila embryo. , 1992, The EMBO journal.

[5]  David H. Sharp,et al.  Model for cooperative control of positional information in Drosophila by bicoid and maternal hunchback. , 1995, The Journal of experimental zoology.

[6]  J. Delosme,et al.  An Efficient Simulated Annealing Schedule : Implementation and Evaluation , 1988 .

[7]  P. Simpson,et al.  Genes of the Enhancer of split and achaete-scute complexes are required for a regulatory loop between Notch and Delta during lateral signalling in Drosophila. , 1996, Development.

[8]  D. Sharp,et al.  Stripe forming architecture of the gap gene system. , 1998, Developmental genetics.

[9]  Hiroaki Kitano,et al.  Simulation of Drosophila embryogenesis , 1998 .

[10]  David H. Sharp,et al.  Multiscale modeling of developmental processes , 1993 .

[11]  Raphael Kopan,et al.  Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain , 1998, Nature.

[12]  M. Levine,et al.  Transcriptional repression in the Drosophila embryo. , 1995, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[13]  J. Davies,et al.  Molecular Biology of the Cell , 1983, Bristol Medico-Chirurgical Journal.

[14]  M. Levine,et al.  Regulation of two pair-rule stripes by a single enhancer in the Drosophila embryo. , 1996, Developmental biology.

[15]  M. Frasch,et al.  Complementary patterns of even-skipped and fushi tarazu expression involve their differential regulation by a common set of segmentation genes in Drosophila. , 1987, Genes & development.

[16]  E Mjolsness,et al.  A gene network approach to modeling early neurogenesis in Drosophila. , 1998, Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

[17]  Jimmy Kwok-Ching Lam,et al.  An efficient simulated annealing schedule , 1988 .

[18]  Hiroaki Kitano,et al.  A method to reconstruct genetic networks applied to the development of Drosophila 's eye , 1998 .

[19]  Julian Lewis,et al.  Neurogenic genes and vertebrate neurogenesis , 1996, Current Opinion in Neurobiology.

[20]  Jimmy Lam An Efficient Simulated Annealing Schedule: Derivation , 1988 .

[21]  David H. Sharp,et al.  A connectionist model of development. , 1991, Journal of theoretical biology.

[22]  Claude Desplan,et al.  Synergy between the hunchback and bicoid morphogens is required for anterior patterning in Drosophila , 1994, Cell.

[23]  T. L. Hill Cooperativity Theory in Biochemistry: Steady-State and Equilibrium Systems , 2011 .

[24]  E. Mjolsness,et al.  Probing the dynamics of cell differentiation in a model of Drosophila neurogenesis , 1998 .

[25]  David H. Sharp,et al.  Mechanism of eve stripe formation , 1995, Mechanisms of Development.

[26]  E. Davidson,et al.  Genomic cis-regulatory logic: experimental and computational analysis of a sea urchin gene. , 1998, Science.