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 (a) 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 (b). 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 (c). More recently, we have shown that tan, encoding an enzyme involved in melanin production, is a major effector of this network (d). Our aim is to complete this network and to highlight sub-components of developmental plasticity.

(a) Debat, V. et al. (2011) PLoS Genet 7, e1002314

(b) Coléno-Costes, A. et al. (2012) PLoS Genet 8, e1003006

(c) Gibert, J-M. et al. (2007) PLoS Genet 3, e30

(d) Gibert et al. (2016) PLoS Genet 12, e1006218


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, then, 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.


A transcriptional cyclin, Cyclin G, participates in growth homeostasis1. Indeed, the over-expression of this cyclin in a population of isogenic flies grown in a standardized environment increase organ fluctuating asymmetry, a stochastic asymmetry resulting from disruption of growth homeostasis1. We have used Cyclin G mis-expression as a sensitized system to identify the genetic and epigenetic bases of growth homeostasis (large scale screen and candidate gene approach). Cyclin G interacts with several factors known to model the epigenome. Indeed, it interacts genetically with the chromatin complexes Polycomb and Trithorax and physically with two of their cofactors, Corto and ASX2. We have shown recently that Cyclin G interacts with particular Polycomb complexes in the control of growth homeostasis. Another original result obtained in our team is the role of a ribosomal protein, RPL12, in the control of gene transcription3. This function is linked to the direct interaction between the chromodomain of Corto and a methylated form of RPL12 (RPL12K3me3). Through RNA-seq experiments, we have shown that Corto, RPL12 and Cyclin G regulate the expression of genes involved in ribosome biogenesis. Thus, a network centered on these three nodes might maintain growth homeostasis through an epigenetic control of ribosome biogenesis. Currently, we are identifying the genetic and physical interactors of these nodes to extend the network.

We have identified a few members of a gene regulatory network that controls pigmentation and is sensitive to temperature4. To complete this network, we have first analysed the transcriptome of the posterior abdomen epithelium from females grown at different temperatures (pupae and young aduts). These experiments have revealed that the gene tan, encoding an enzyme involved in melanin production, is a major effector of this network and that the activity of a tan enhancer, t-MSE, is modulated by temperature5. The thermal plasticity of tan expression is correlated with the level of the active epigenetic mark H3K4me3 on its promoter. This mark might represent a universal plasticity mark as similar results were obtained in other organisms. We have shown that Trithorax is the enzyme apposing this mark5. Through complementary experiments (yeast simple hybrid, genetic screen targeting transcription factors and chromatin regulators, reaction norms), we have identified several regulators of tan that are sensitive to temperature. We are currently performing epistasis experiments with these genes to build the regulatory gene network of pigmentation plasticity. Our final goal is to model this network.

1Debat et al. (2011) PLoS Genet 7, e1002314

2Dupont et al. (2015) Epigenetics & Chromatin 8, 18

3Coléno-Costes et al. (2012) PLoS Genet 8, e1003006

4Gibert et al. (2007) PLoS Genet 3, e30

5Gibert et al. (2016) PLoS Genet 12, e1006218

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.