A Toggle-Switch and a Feed-Forward Loop Engage in the Control of the Drosophila Retinal Determination Gene Network
|Author/s||Sánchez Aragón, Máximo
Cantisán Gómez, Julia
Luque, Carlos M.
Brás Pereira, Catarina
Lopes, Carla S.
Lemos Fernández, María del Carmen
|Department||Universidad de Sevilla. Departamento de Física de la Materia Condensada|
|Abstract||Dipterans show a striking range of eye sizes, shapes, and functional specializations.
Their eye is of the compound type, the most frequent eye architecture in nature. The
development of this compound eye has been most ...
Dipterans show a striking range of eye sizes, shapes, and functional specializations. Their eye is of the compound type, the most frequent eye architecture in nature. The development of this compound eye has been most studied in Drosophila melanogaster. The early development of the Drosophila eye is under the control of a gene regulatory network of transcription factors and signaling molecules called the retinal determination gene network (RDGN). Nodes in this network have been found to be involved not only in the development of different eye types in invertebrates and vertebrates, but also of other organs. Here we have analyzed the network properties in detail. First, we have generated quantitative expression profiles for a number of the key RDGN transcription factors, at a single-cell resolution. With these profiles, and applying a correlation analysis, we revisited several of the links in the RDGN. Our study uncovers a new link, that we confirm experimentally, between the transcription factors Hth/Meis1 and Optix/Six3 and indicates that, at least during the period of eye differentiation, positive feedback regulation from Eya and Dac on the Pax6 gene Ey is not operating. From this revised RDGN we derive a simplified gene network that we model mathematically. This network integrates three basic motifs: a coherent feedforward loop, a toggle-switch and a positive autoregulation which, together with the input from the Dpp/BMP2 signaling molecule, recapitulate the gene expression profiles obtained experimentally, while ensuring a robust transition from progenitor cells into retinal precursors.
|Funding agencies||Ministerio de Economía y Competitividad (MINECO). España
European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Agencia Estatal de Investigación. España
|Citation||Sánchez Aragón, M., Cantisán Gómez, J., Luque, C.M., Brás Pereira, C., Lopes, C.S., Lemos Fernández, M.d.C. y Casares, F. (2019). A Toggle-Switch and a Feed-Forward Loop Engage in the Control of the Drosophila Retinal Determination Gene Network. Frontiers in Ecology and Evolution, 7, 221.|