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Modeling the Drosophila gene cluster regulation network for muscle development.

ABSTRACT: The development of accurate and reliable dynamical modeling procedures that describe the time evolution of gene expression levels is a prerequisite to understanding and controlling the transcription process. We focused on data from DNA microarray time series for 20 Drosophila genes involved in muscle development during the embryonic stage. Genes with similar expression profiles were clustered on the basis of a translation-invariant and scale-invariant distance measure. The time evolution of these clusters was modeled using coupled differential equations. Three model structures involving a transcription term and a degradation term were tested. The parameters were identified in successive steps: network construction, parameter optimization, and parameter reduction. The solutions were evaluated on the basis of the data reproduction and the number of parameters, as well as on two biology-based requirements: the robustness with respect to parameter variations and the values of the expression levels not being unrealistically large upon extrapolation in time. Various solutions were obtained that satisfied all our evaluation criteria. The regulatory networks inferred from these solutions were compared with experimental data. The best solution has half of the experimental connections, which compares favorably with previous approaches. Biasing the network toward the experimental connections led to the identification of a model that is only slightly less good on the basis of the evaluation criteria. The non-uniqueness of the solutions and the variable agreement with experimental connections were discussed in the context of the different hypotheses underlying this type of approach.

SUBMITTER: Haye A

PROVIDER: S-EPMC3940846 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Modeling the Drosophila gene cluster regulation network for muscle development.

Haye Alexandre A Albert Jaroslav J Rooman Marianne M

PloS one 20140303 3

The development of accurate and reliable dynamical modeling procedures that describe the time evolution of gene expression levels is a prerequisite to understanding and controlling the transcription process. We focused on data from DNA microarray time series for 20 Drosophila genes involved in muscle development during the embryonic stage. Genes with similar expression profiles were clustered on the basis of a translation-invariant and scale-invariant distance measure. The time evolution of thes ...[more]

PMID: 24594656

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Project description:BackgroundThe pistil is an essential part of flowers that functions in the differentiation of the sexes and reproduction in plants. The stigma on the pistil can accept pollen to allow fertilization and seed development. Papaya (Carica papaya L.) is a dioecious plant, where female flowers exhibit normal pistil, while the male flowers exhibit aborted pistil at a late stage of pistil development.ResultsThe developmental stages of papaya pistil were analyzed after first dividing it into slices representing the primordium stage 1 (S1), the pre-meiotic stages S2, post-meiotic stage S3, and the mitotic stage S4. The SS scoring algorithm analysis of genes preferentially expressed at different stages revealed differentially expressed genes between male and female flowers. A transcription factor regulatory network for each stage based on the genes that are differentially expressed between male and female flowers was constructed. Some transcription factors related to pistil development were revealed based on the analysis of regulatory networks such as CpAGL11, CpHEC2, and CpSUPL. Based on the specific expression of genes, constructed a gene regulatory subnetwork with CpAGL11-CpSUPL-CpHEC2 functioning as the core. Analysis of the functionally enriched terms in this network reveals several differentially expressed genes related to auxin/ brassinosteroid signal transduction in the plant hormone signal transduction pathway. At the same time, significant differences in the expression of auxin and brassinosteroid synthesis-related genes between male and female flowers at different developmental stages were detected.ConclusionsThe pistil abortion of papaya might be caused by the lack of expression or decreased expression of some transcription factors and hormone-related genes, affecting hormone signal transduction or hormone biosynthesis. Analysis of aborted and normally developing pistil in papaya provided new insights into the molecular mechanism of pistil development and sex differentiation in dioecious papaya.

Project description:Within the Drosophila embryo, two related bHLH-PAS proteins, Single-minded and Trachealess, control development of the central nervous system midline and the trachea, respectively. These two proteins are bHLH-PAS transcription factors and independently form heterodimers with another bHLH-PAS protein, Tango. During early embryogenesis, expression of Single-minded is restricted to the midline and Trachealess to the trachea and salivary glands, whereas Tango is ubiquitously expressed. Both Single-minded/Tango and Trachealess/Tango heterodimers bind to the same DNA sequence, called the CNS midline element (CME) within cis-regulatory sequences of downstream target genes. While Single-minded/Tango and Trachealess/Tango activate some of the same genes in their respective tissues during embryogenesis, they also activate a number of different genes restricted to only certain tissues. The goal of this research is to understand how these two related heterodimers bind different enhancers to activate different genes, thereby regulating the development of functionally diverse tissues. Existing data indicates that Single-minded and Trachealess may bind to different co-factors restricted to various tissues, causing them to interact with the CME only within certain sequence contexts. This would lead to the activation of different target genes in different cell types. To understand how the context surrounding the CME is recognized by different bHLH-PAS heterodimers and their co-factors, we identified and analyzed novel enhancers that drive midline and/or tracheal expression and compared them to previously characterized enhancers. In addition, we tested expression of synthetic reporter genes containing the CME flanked by different sequences. Taken together, these experiments identify elements overrepresented within midline and tracheal enhancers and suggest that sequences immediately surrounding a CME help dictate whether a gene is expressed in the midline or trachea.

Dataset Information

Modeling the Drosophila gene cluster regulation network for muscle development.

Publications

Modeling the Drosophila gene cluster regulation network for muscle development.

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