Growth control in the eye disc by the cytokine Unpaired.

A fundamental question in developmental biology is how organ size is controlled. We have previously shown that the area growth rate in the eye primordium declines inversely proportionally to the increase in its area. How the observed reduction in the growth rate is achieved is unknown.

A Model of the Spatio-temporal Dynamics of Drosophila Eye Disc Development.

Patterning and growth are linked during early development and have to be tightly controlled to result in a functional tissue or organ. During the development of the Drosophila eye, this linkage is particularly clear: the growth of the eye primordium mainly results from proliferating cells ahead of the morphogenetic furrow (MF), a moving signaling wave that sweeps across the tissue from the posterior to the anterior side, that induces proliferating cells anterior to it to differentiate and become cell cycle quiescent in its wake. Therefore, final eye disc size depends on the proliferation rate of undifferentiated cells and on the speed with which the MF sweeps across the eye disc.

A quantitative analysis of growth control in the Drosophila eye disc.

The size and shape of organs is species specific, and even in species in which organ size is strongly influenced by environmental cues, such as nutrition or temperature, it follows defined rules. Therefore, mechanisms must exist to ensure a tight control of organ size within a given species, while being flexible enough to allow for the evolution of different organ sizes in different species. We combined computational modeling and quantitative measurements to analyze growth control in the Drosophila eye disc.

Read-Out of Dynamic Morphogen Gradients on Growing Domains.

Quantitative data from the Drosophila wing imaginal disc reveals that the amplitude of the Decapentaplegic (Dpp) morphogen gradient increases continuously. It is an open question how cells can determine their relative position within a domain based on a continuously increasing gradient. Here we show that pre-steady state diffusion-based dispersal of morphogens results in a zone within the growing domain where the concentration remains constant over the patterning period.

Axis Patterning by BMPs: Cnidarian Network Reveals Evolutionary Constraints.

BMP signaling plays a crucial role in the establishment of the dorso-ventral body axis in bilaterally symmetric animals. However, the topologies of the bone morphogenetic protein (BMP) signaling networks vary drastically in different animal groups, raising questions about the evolutionary constraints and evolvability of BMP signaling systems. Using loss-of-function analysis and mathematical modeling, we show that two signaling centers expressing different BMPs and BMP antagonists maintain the secondary axis of the sea anemone Nematostella.

Identification of constrained cancer driver genes based on mutation timing.

Cancer drivers are genomic alterations that provide cells containing them with a selective advantage over their local competitors, whereas neutral passengers do not change the somatic fitness of cells. Cancer-driving mutations are usually discriminated from passenger mutations by their higher degree of recurrence in tumor samples. However, there is increasing evidence that many additional driver mutations may exist that occur at very low frequencies among tumors.

Dynamic scaling of morphogen gradients on growing domains.

Developmental mechanisms are highly conserved, yet act in embryos of very different sizes. How scaling is achieved has remained elusive. Here we identify a generally applicable mechanism for dynamic scaling on growing domains and show that it quantitatively agrees with data from the Drosophila wing imaginal disc.

Simulating tissue morphogenesis and signaling.

During embryonic development tissue morphogenesis and signaling are tightly coupled. It is therefore important to simulate both tissue morphogenesis and signaling simultaneously in in silico models of developmental processes. The resolution of the processes depends on the questions of interest.