Epigenetic control of developmental homeostasis and plasticity

How do developmental processes resist to genetic, stochastic and environmental variation, i.e. how is developmental homeostasis maintained? How are phenotypes modulated in response to changes of the environment, i.e. how is developmental plasticity controlled? To answer these questions, we combine morphometric description of an organ and analysis of its transcriptome and epigenome.

We address two questions: How are genetic, environmental and stochastic variations buffered during development, i.e. how is developmental homeostasis achieved? How do environmental changes induce phenotype modifications, i.e. how is developmental plasticity controlled? Our recent works suggest a major role for epigenetic transcriptional regulation in these two facets of phenotypic variability. We combine morphometric description and genome-wide transcriptome and epigenome analyses of organs in wild type or mutant contexts.

To address developmental homeostasis, we use the Drosophila wing, which allows accurate measurements of size and shape. We have highlighted two important mechanisms of growth homeostasis. First, the buffering of stochastic variations of growth involves a transcriptional cyclin, Cyclin G. Second, ribosome biogenesis might be stabilized by coordination of Ribosomal Protein and Ribosomal Biogenesis gene expression by Ribosomal Protein L12. Starting from these two processes, we are identifying gene networks that underlie developmental homeostasis.

As a model of developmental plasticity, we use the posterior abdomen of Drosophila females, whose pigmentation varies with developmental temperature. We have previously identified a temperature-sensitive gene regulatory network that controls female abdominal pigmentation. More recently, we have shown that tan, encoding an enzyme involved in melanin production, is a major effector of this network. Our aim is to complete this network and to highlight sub-components of developmental plasticity.


Our team focuses on the two sides of phenotypic variablity, developmental homeostasis (i.e. maintenance of the phenotype despite genetic, environmental and stochastic perturbations) and developmental plasticity (i.e. the capacity of a developing organism to produce different phenotypes from a single genotype depending on environmental conditions). The identification of mechanisms underlying developmental homeostasis and plasticity is fundamental in developmental as well as evolutionary biology as selection operates on phenotypes. Furthermore, developmental homeostasis and plasticity can be involved in adaptation of organisms to their environment. Our studies aim at identifying the genetic and epigenetic bases of developmental homeostasis and plasticity in Drosophila melanogaster. We study two model organs: the wing, whose flat and stereotyped structure allows a quantitative analysis of variation in size and shape, and the epithelium of the posterior abdomen of female, whose pigmentation is particularly sensitive to temperature variations. We analyse the transcriptome and epigenome of these organs in different genetic and environmental conditions. Our results show a substantial role of the epigenome in developmental homeostasis and plasticity. Using these genetic and epigenomic data, we are building gene networks underlying developmental homeostasis and plasticity. We plan to model these networks in order to understand the mechanisms of homeostasis and plasticity. Our results have already led to the characterization of several essential actors of these mechanisms.


Growth homeostasis participates in the robustness of organ size and is therefore paramount for the development of symmetric organs in bilaterians. We have shown the importance of the transcriptional cyclin, Cyclin G in this process in Drosophila 1. Indeed, the expression of a potentially more stable form of this cyclin increases organ fluctuating asymmetry, showing that it decreases the robustness of organ size1. We use the deregulation of Cyclin G to investigate the genetic and epigenetic bases of growth homeostasis. Cyclin G interacts with several factors known to shape the epigenome. In particular, it binds the Enhancer of Trithorax and Polycomb (Corto) and ASX, a sub-unit of the PR-DUB Polycomb complex2. The interaction between Cyclin G and the Polycomb complexes PR-DUB and PRC1 is important for the robustness of organ size pointing to a role of transcriptional regulation in growth homeostasis3. Cyclin G and Corto interact with the ribosomal protein RPL12 which has an extra-ribosomal activity and controls transcription4. The Corto chromodomain directly interacts with a methylated form of RPL12 (RPL12K3me3)4. This methylation could regulate RPL12 transcriptional activity, hence our interest to identify the enzyme apposing this mark. We have recently identified dSETD4 as the RPL12 lysine 3 methyl transferase. Strikingly, Corto, RPL12 and Cyclin G shared transcriptional gene targets mostly involved in ribosome biogenesis. Wing fluctuating asymmetry correlates with an increase in the expression of genes involved in translation, notably genes encoding ribosomal proteins, and a decrease in the expression of genes involved in mitochondrial activity and metabolism3. Thus, we are testing the hypothesis that a network centred on the three proteins Cyclin G, Corto and RpL12 ensures growth homeostasis via a coordinated epigenetic control of ribosome biogenesis, mitochondrial activity and metabolism. Identification of the interactors of these three proteins and their importance in organ symmetry will allow us to build a network underlying growth homeostasis.

In order to dissect the mechanisms underlying phenotypic plasticity, we have first identified the core of a regulatory gene network controlling the plasticity of pigmentation in response to temperature in Drosophila5. To complement this network, we have performed transcriptional analyses of the epithelium from females grown at different temperatures. These experiments have revealed that the gene tan, encoding a pigmentation enzyme, is a major effector of this network. Furthermore, the activity of the tan enhancer t-MSE is modulated by temperature6. The gene yellow, encoding another pigmentation enzyme is also involved pigmentation plasticity7 however to a lesser extent. The expression of bab1 and bab2, two tan regulators, is sensitive to temperature8. The transcriptional plasticity of tan is therefore, at least partly, a consequence of that of bab1 and bab2. Interestingly, the activity of an enhancer of bab1 and bab2 genes is also sensitive to temperature and this partly results from its regulation by the Hox protein Abdominal-B8. Therefore, the genes bab1, bab2 and Abd-B belong together with tan to a gene network involved in pigmentation plasticity. Through complementary experiments (yeast one hybrid screen, genetic screen targeting transcription factors and chromatin regulators, reaction norms), we have identified other genes involved in abdominal pigmentation and, among them, tan regulators that are sensitive to temperature. We are positioning these genes in the core network by epistasis experiments. Our goal is then to model this network. In addition, we have shown that genetic variation in the enhancers of bab1, bab2 and tan modulate pigmentation in natural populations8,9,10. The fact that these enhancers mediate the response to the environment6,8 and accumulate genetic variation that impacts it leads to the fundamental question of the links between phenotypic plasticity and evolution11. Lastly, we have shown the role of developmental constraints linked to the patterning of flight muscles on pigmentation patterns12. Such constraints could also have an impact on evolution.

  • 1Debat, Bloyer et al. (2011) PLoS Genet 7, e1002314
  • 2Dupont et al. (2015) Epigenetics & Chromatin 8, 18
  • 3Dardalhon-Cuménal, Deraze et al. (2018) PLoS Genet 14(7) e1007498
  • 4Coléno-Costes et al. (2012) PLoS Genet 8, e1003006
  • 5Gibert et al. (2007) PLoS Genet 3, e30
  • 6Gibert, Mouchel-Vielh et al. (2016) PLoS Genet 12, e1006218
  • 7Gibert et al. (2017) Sci Rep 7 :43370
  • 8De Castro et al. (2018) PLoS Genet 14(8) e1007573
  • 9Gibert, Blanco et al. (2017) Genome Biol 18(1)
  • 10Endler et al. (2018) Mol Ecol 27
  • 11Gibert (2017) Dev Genes Evol : Aug 6
  • 12Gibert et al. (2018) Sci Rep 8(1) : 5328

Future directions

Do developmental homeostasis and plasticity use common processes? If this is the case, what could be the consequences in a fluctuating environment? What are the environmental factors that affect them? are the questions that will motivate our research in the future.


  • Dr. Vincent Debat, UMR7205 Institut de Systématique, Evolution, Biodiversité (ISYEB) MNHN, Paris - Control of developmental noise, geometric morphometrics.
  • Dr. Bart Deplancke, EPFL, Lausanne, Suisse - Identification of direct regulators of tan using automated yeast simple hybrid.
  • Pr. Stéphane Le Crom, Genomic Paris Centre, ENS, Paris - Transcriptomic and epigenomic analyses. 
  • Pr. Bruno Lemaître, EPFL, Lausanne, Suisse - Pigmentation and immunity.
  • Dr. Raphaël Margueron, UMR3215 Developmental Biology and Genetics, Institut Curie, Paris – The Drosophila RPL12 methyltransferase.
  • Dr. Christian Schlötterer (Vetmeduni, Vienna, Austria): Natural variation for pigmentation.
  • Pr. Hédi Soula, Centre de Recherche des Cordeliers, UPMC - Modeling pigmentation gene networks.