title: The role of regulated mRNA stability in establishing bicoid morphogen gradient in Drosophila embryonic development.
abstract: The Bicoid morphogen is amongst the earliest triggers of differential spatial pattern of gene expression and subsequent cell fate determination in the embryonic development of Drosophila. This maternally deposited morphogen is thought to diffuse in the embryo, establishing a concentration gradient which is sensed by downstream genes. In most model based analyses of this process, the translation of the bicoid mRNA is thought to take place at a fixed rate from the anterior pole of the embryo and a supply of the resulting protein at a constant rate is assumed. Is this process of morphogen generation a passive one as assumed in the modelling literature so far, or would available data support an alternate hypothesis that the stability of the mRNA is regulated by active processes? We introduce a model in which the stability of the maternal mRNA is regulated by being held constant for a length of time, followed by rapid degradation. With this more realistic model of the source, we have analysed three computational models of spatial morphogen propagation along the anterior-posterior axis: (a) passive diffusion modelled as a deterministic differential equation, (b) diffusion enhanced by a cytoplasmic flow term; and (c) diffusion modelled by stochastic simulation of the corresponding chemical reactions. Parameter estimation on these models by matching to publicly available data on spatio-temporal Bicoid profiles suggests strong support for regulated stability over either a constant supply rate or one where the maternal mRNA is permitted to degrade in a passive manner.
authors.affiliation: School of Electronics and Computer Science, University of Southampton, Southampton, United Kingdom. wl08r@ecs.soton.ac.uk
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Mahesan
authors.initials: M
authors.lastname: Niranjan
mesh_terms: D000465:Algorithms; D000818:Animals; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013269:Stochastic Processes; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D035501:Uncertainty
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C056478:bcd protein, Drosophila