title: Reverse-engineering post-transcriptional regulation of gap genes in Drosophila melanogaster.
abstract: Systems biology proceeds through repeated cycles of experiment and modeling. One way to implement this is reverse engineering, where models are fit to data to infer and analyse regulatory mechanisms. This requires rigorous methods to determine whether model parameters can be properly identified. Applying such methods in a complex biological context remains challenging. We use reverse engineering to study post-transcriptional regulation in pattern formation. As a case study, we analyse expression of the gap genes Krüppel, knirps, and giant in Drosophila melanogaster. We use detailed, quantitative datasets of gap gene mRNA and protein expression to solve and fit a model of post-transcriptional regulation, and establish its structural and practical identifiability. Our results demonstrate that post-transcriptional regulation is not required for patterning in this system, but is necessary for proper control of protein levels. Our work demonstrates that the uniqueness and specificity of a fitted model can be rigorously determined in the context of spatio-temporal pattern formation. This greatly increases the potential of reverse engineering for the study of development and other, similarly complex, biological processes.
authors.affiliation: EMBL/CRG Research Unit in Systems Biology, Centre de Regulació Genòmica, and Universitat Pombeu Fabra (UPF), Barcelona, Spain ; Institute of Genetics, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Kolja
authors.initials: K
authors.lastname: Becker
authors.forename: Eva
authors.initials: E
authors.lastname: Balsa-Canto
authors.forename: Damjan
authors.initials: D
authors.lastname: Cicin-Sain
authors.forename: Astrid
authors.initials: A
authors.lastname: Hoermann
authors.forename: Hilde
authors.initials: H
authors.lastname: Janssens
authors.forename: Julio R
authors.initials: JR
authors.lastname: Banga
authors.forename: Johannes
authors.initials: J
authors.lastname: Jaeger
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005818:Genetic Engineering / Q000379:methods*; D008957:Models, Genetic; D055550:Protein Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*
chemical_list: D029721:Drosophila Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins