Research groups

Gene regulation and morphogenesis

Fernando Casares, CSIC
Control of organ growth and identity during development and evolution
Fernando Casares, CSIC
Principal Investigator

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Specific Projects

The Casares lab Projects

1- The small eyes: The ocelli and the study of Hh-mediated patterning at high resolution. Adult flies, like most insects, have two eye types. The lateral, compound eye, and the dorsal ocelli –or simple eyes. While the development of the compound eye relies on the extensive proliferation of progenitor cells and a complex differentiation dynamics, involving a number of signaling pathways (see here and below), the formation of the ocelli is simpler. First, the contribution of proliferation is less important. Second, the major signaling pathway involved in controlling the size of the ocelli is that of hedgehog (hh), the founder member of the widely conserved Hh family of morphogens. In the ocelli, one single Hh source specifies and patterns two small adjacent fields of cells, 8-10 cells across. By combining genetics, confocal microscopy (on fixed and life samples), quantitative imaging and modeling we can investigate, in great detail, the interaction between the Hh morphogen and the gene regulatory network that it steers. By investigating this morphogen-gene network interaction we are further exploring the possibilities for morphological evolution that this system allows, as a model to understand the relation between developmental processes and morphological plasticity. We collaborate on this project with physicists Daniel Aguilar-Hidalgo and David G-Míguez. In addition, we are using the operational principles of the ocellar neural network to inspire the design of flight control devices to be implemented on small flying robots (“MAVs”, after micro aerial vehicles), which have the same flying problems as small flying insects -in collaboration with the Robotics, Vision and Control lab of Luis Merino and insect neurophysiologist Antonio Prado.


2- The large eyes: Rules integrating growth and differentiation dynamics. The compound eye is formed by hundreds of unit eyes, called ommatidia. In contrast with the ocelli, the development of the compound eye requires the vigorous proliferation of eye progenitors. Differentiation is driven by a signaling wave, that sweeps across the epithelium that consittutes the eye primordium. The wavefront of this wave is detected as an indentation of the epithelium, called the morphogenetic furrow. As the signals emanating from the wavefront reach progenitor cells, these exit the cell cycle and start differentiating into ommatidia –which produce more progenitor-recruiting signals, generating a feedforward mechanisms that makes the wave "roll" forward. Therefore, the final size of the eye depends on the integration of proliferation, differentiation and the geometry of the primordium. By combining quantitative imaging, genetics and mathematical modeling we are deriving rules that describe the relationships between proliferation and differentiation dynamics so that eyes reach a final, species-specific size. We are further investigating how related Drosophila species manage to generate eyes of different sizes. We are working in collaboration with the groups of mathematician Dagmar Iber and of biologists Bassem Hassan and Alistair McGregor.


3- The physical component in size control: mechanical feedback. Tissues are biological matter and, as such, obey the laws of physics. Therefore, as organs develop, cells generate and experience physical forces. Using the Drosophila eye as model, we are investigating the forces that build up during eye development and explore to what extent these forces impact the growth and differentiation dynamics that determine the eye final size.


4- Making even larger eyes: the eyes of the hoverfly Episyrphus. Hoverflies (also known as flower flies) have eyes composed not of hundreds, but of thousands of ommatidia. When we think about what we know on how Drosophila flies make their eyes, it seems to us that hoverflies might be doing things quite differently. We are currently investigating how one hoverfly, Episyrphus balteatus, develops its huge eyes. We are describing the growth and differentiation parameters of these eyes during development and will analyze the developmental gene expression profile to find out what the mechanisms underlying the formation of these oversized eyes are. The fact that hoverflies are an old dipteran lineage makes us think that perhaps Episyrphus will tell us things about how eyes were made in primitive flies. Biologist Karl Wotton has helped us in setting up our hoverfly culture.



5- New and exaggerated: The dorsal turban eyes of the mayfly Cloeon. Mayflies (Ephemeroptera) are basal insects –and thus their origin is much older than that of flies. Mayflies are great innovators. For example, Mayflies were the first insects in the fossil record to show the development of wings. Prior to them, insects were “apterygotes”. Within mayflies, some groups show a remarkable sexual dimorphism: while females have the two standard eye sets (compound eyes, located laterally, and ocelli, on the forefront), males develop an extra pair of eyes, stemming from the dorsal head, that are huge. These are called “turban” eyes and often cover the head of the males like a dome. One of these species is Cloeon dipterum. We believe that Cloeon male larvae reactivate the eye gene regulatory network under the control of the sex-determination cascade, generating this novel eye type. But, how? Cloeon offers the possibility of investigating how evolutionary innovations arise and, more specifically, how gene network rewiring generates novel organs –in this case, so extraordinary as the turban eyes. Javier Alba-Tercedor is helping us in understanding how female and male head development differ during development, using microCT (to see a sampler of Dr. Alba-Tercedor’s amazing work, check out this). To characterize Cloeon’s genome, we are collaborating with Michael Monaghan. Working together with the computational biology groups of Stein Aerts and Damian Devos we are characterizing the gene expression differences between males and females as their nymphs develop their visual systems.