Core regulatory network motif underlies the ocellar complex patterning in Drosophila melanogaster

arXiv:1404.4554v5During organogenesis, developmental programs governed by Gene Regulatory Networks (GRN) define the functionality, size and shape of the different constituents of living organisms. Robustness, thus, is an essential characteristic that GRNs need to fulfill in order to maintain viability and reproducibility in a species. In the present work we analyze the robustness of the patterning for the ocellar complex formation in Drosophila melanogaster fly. We have systematically pruned the GRN that drives the development of this visual system to obtain the minimum pathway able to satisfy this pattern. We found that the mechanism underlying the patterning obeys to the dynamics of a 3-nodes network motif with a double negative feedback loop fed by a morphogenetic gradient that triggers the inhibition in a French flag problem fashion. A Boolean modeling of the GRN confirms robustness in the patterning mechanism showing the same result for different network complexity levels. Interestingly, the network provides a steady state solution in the interocellar part of the patterning and an oscillatory regime in the ocelli. This theoretical result predicts that the ocellar pattern may underlie oscillatory dynamics in its genetic regulation.This work is partially financed by Junta de Andalucía (FQM-122) to A. Córdoba and by the Spanish Ministry for Science and Innovation (MICINN/MINECO) and Feder Funds through grants BFU2012-34324 to F. Casares (CABD, Seville, Spain) and Consolider Ingenio-2010 ‘From Genes to Shape’ (CSD 2007-008), of which F. Casares was a participant researcher.Peer Reviewe

Critical Point in Self-Organized Tissue Growth

We present a theory of pattern formation in growing domains inspired by biological examples of tissue development. Gradients of signaling molecules regulate growth, while growth changes these graded chemical patterns by dilution and advection. We identify a critical point of this feedback dynamics, which is characterized by spatially homogeneous growth and proportional scaling of patterns with tissue length. We apply this theory to the biological model system of the developing wing of the fruit fly \textit{Drosophila melanogaster} and quantitatively identify signatures of the critical point.Comment: 5 pages, 3 figure

Evolutionary Dynamics in Gene Networks and Inference Algorithms

Dynamical interactions among sets of genes (and their products) regulate developmental processes and some dynamical diseases, like cancer. Gene regulatory networks (GRNs) are directed networks that define interactions (links) among different genes/proteins involved in such processes. Genetic regulation can be modified during the time course of the process, which may imply changes in the nodes activity that leads the system from a specific state to a different one at a later time (dynamics). How the GRN modifies its topology, to properly drive a developmental process, and how this regulation was acquired across evolution are questions that the evolutionary dynamics of gene networks tackles. In the present work we review important methodology in the field and highlight the combination of these methods with evolutionary algorithms. In recent years, this combination has become a powerful tool to fit models with the increasingly available experimental data.Junta de Andalucía FQM-12

Core regulatory network motif underlies the ocellar complex patterning in Drosophila melanogaster

During organogenesis, developmental programs governed by Gene Regulatory Networks (GRN) define the functionality, size and shape of the different constituents of living organisms. Robustness, thus, is an essential characteristic that GRNs need to fulfill in order to maintain viability and reproducibility in a species. In the present work we analyze the robustness of the patterning for the ocellar complex formation in Drosophila melanogaster fly. We have systematically pruned the GRN that drives the development of this visual system to obtain the minimum pathway able to satisfy this pattern. We found that the mechanism underlying the patterning obeys to the dynamics of a 3-nodes network motif with a double negative feedback loop fed by a morphogenetic gradient that triggers the inhibition in a French flag problem fashion. A Boolean modeling of the GRN confirms robustness in the patterning mechanism showing the same result for different network complexity levels. Interestingly, the network provides a steady state solution in the interocellar part of the patterning and an oscillatory regime in the ocelli. This theoretical result predicts that the ocellar pattern may underlie oscillatory dynamics in its genetic regulation.Junta de Andalucía FQM-122España, Ministerio de Ciencia e Innovación MICINN / MINECOFondos Federales BFU2012-34324Consolider Ingenio-2010 CSD 2007-00

It’s not all abundance: Detectability and accessibility of food also explain breeding investment in long-lived marine animals

Large-scale climatic indices are extensively used as predictors of ecological processes, but the mechanisms and the spatio-temporal scales at which climatic indices influence these processes are often speculative. Here, we use long-term data to evaluate how a measure of individual breeding investment (the egg volume) of three long-lived and long-distance-migrating seabirds is influenced by i) a large-scale climatic index (the North Atlantic Oscillation) and ii) local-scale variables (food abundance, foraging conditions, and competition). Winter values of the North Atlantic Oscillation did not correlate with local-scale variables measured in spring, but surprisingly, both had a high predictive power of the temporal variability of the egg volume in the three study species, even though they have different life-history strategies. The importance of the winter North Atlantic Oscillation suggests carry-over effects of winter conditions on subsequent breeding investment. Interestingly, the most important local-scale variables measured in spring were associated with food detectability (foraging conditions) and the factors influencing its accessibility (foraging conditions and competition by density-dependence). Large-scale climatic indices may work better as predictors of foraging conditions when organisms perform long distance migrations, while local-scale variables are more appropriate when foraging areas are more restricted (e.g. during the breeding season). Contrary to what is commonly assumed, food abundance does not directly translate into food intake and its detectability and accessibility should be considered in the study of food-related ecological processes.En prensa4,41

A Hh-driven gene network controls specification, pattern and size of the Drosophila simple eyes

During development, extracellular signaling molecules interact with intracellular gene networks to control the specification, pattern and size of organs. One such signaling molecule is Hedgehog (Hh). Hh is known to act as a morphogen, instructing different fates depending on the distance to its source. However, how Hh, when signaling across a cell field, impacts organ-specific transcriptional networks is still poorly understood. Here, we investigate this issue during the development of the Drosophila ocellar complex. The development of this sensory structure, which is composed of three simple eyes (or ocelli) located at the vertices of a triangular patch of cuticle on the dorsal head, depends on Hh signaling and on the definition of three domains: two areas of eya and so expression - the prospective anterior and posterior ocelli - and the intervening interocellar domain. Our results highlight the role of the homeodomain transcription factor engrailed (en) both as a target and as a transcriptional repressor of hh signaling in the prospective interocellar region. Furthermore, we identify a requirement for the Notch pathway in the establishment of en maintenance in a Hh-independent manner. Therefore, hh signals transiently during the specification of the interocellar domain, with en being required here for hh signaling attenuation. Computational analysis further suggests that this network design confers robustness to signaling noise and constrains phenotypic variation. In summary, using genetics and modeling we have expanded the ocellar gene network to explain how the interaction between the Hh gradient and this gene network results in the generation of stable mutually exclusive gene expression domains. In addition, we discuss some general implications our model may have in some Hh-driven gene networks.Ministerio de Ciencias e Innovacion BFU2009-07044 FIS2008-04120Junta de Andalucía CVI 265

A model of the spatio-temporal dynamics of drosophila eye disc development

Patterning and growth are linked during early development and have to be tightly controlled to result in a functional tissue or organ. During the development of the Drosophila eye, this linkage is particularly clear: the growth of the eye primordium mainly results from proliferating cells ahead of the morphogenetic furrow (MF), a moving signaling wave that sweeps across the tissue from the posterior to the anterior side, that induces proliferating cells anterior to it to differentiate and become cell cycle quiescent in its wake. Therefore, final eye disc size depends on the proliferation rate of undifferentiated cells and on the speed with which the MF sweeps across the eye disc. We developed a spatio-temporal model of the growing eye disc based on the regulatory interactions controlled by the signals Decapentaplegic (Dpp), Hedgehog (Hh) and the transcription factor Homothorax (Hth) and explored how the signaling patterns affect the movement of the MF and impact on eye disc growth. We used published and new quantitative data to parameterize the model. In particular, two crucial parameter values, the degradation rate of Hth and the diffusion coefficient of Hh, were measured. The model is able to reproduce the linear movement of the MF and the termination of growth of the primordium. We further show that the model can explain several mutant phenotypes, but fails to reproduce the previously observed scaling of the Dpp gradient in the anterior compartmen