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