Research

Our research seeks to understand how genetic variation is translated through development into phenotypes, and how developmental phenotypes evolve. Of particular interest is in the interplay between genetic variation, developmental robustness, and evolution. We combine classical techniques – embryology and genetics – with advanced imaging, high-throughput sequencing and computation, primarily in the model system of Drosophila.

One of the most remarkable aspects of development is that it is a robust process, in that development produces stereotyped outcomes despite encountering variation in ontogeny. This variation can come in many forms, including genetic, environmental, and stochastic sources, and there are a variety of types of mechanisms that suppress the effect of this variation on the resulting phenotype of the organism. This presents an interesting tension between the robustness of development and the process of evolution, for the variation in phenotype suppressed by robustness is the raw material upon which evolutionary processes act. We pursue a number of different projects to understand these fundamental questions:

Robustness of development to variation in gene dose

We study variation in X chromosome dose as one model for exploring robustness in development. There are specific mechanisms in many organisms to compensate for difference in sex chromosome dosage. In Drosophila, the characterized dosage compensation mechanism (MSL-mediated dosage compensation) is established several hours after the embryo starts transcribing from the X chromosomes, yet we discovered that some genes are still compensated, by some other mechanism (which we are investigating), during this time. In studying gene expression levels in female and male embryos in early development, we are creating a catalog of genes on sex chromosomes that are always dosage compensated, or are never dosage compensated. We will use these candidates to investigate whether compensation is a proxy for developmental constraint, and if so, what kinds of genes and developmental processes are subject to the most constraint.

Variation in embryo “starting state”

Early animal development is dependent on mRNAs and proteins placed into eggs by females during oogenesis. These maternally deposited molecules play a critical role in all early embryonic processes, and determine the “starting state” for the regulatory processes that drive embryogenesis. The proteins and mRNAs deposited by D. melanogaster are well characterized, but despite the importance of these factors, and their potential to drive differences in developmental processes, we have no knowledge of the extent of natural variation in maternally deposited mRNAs within or between species. We are using RNA-Seq to characterize embryonic mRNA pools within and between species, investigating how it affects developmental processes and phenotypic outcomes, what evolutionary correlates or trade-offs may be involved, and how the dynamics of the maternal-zygotic handoff of developmental control might be subject to evolutionary conflict. We will also study the genetic mechanisms underlying the evolution in maternal deposition.

Evolution in body plan

Some variation is able to escape developmental robustness to propagate through development. Insects are segmented animals, and the process of segmentation has been demonstrated to be robust. Yet adults have some variation in segment size and shape. We are developing a high-throughput imaging-based screen to characterize segment allometry in Drosophila larvae, both within and between species. We will investigate the genetic basis of variation in segment allometry, and taking advantage of the well-characterized segmentation gene network, we will pursue the ultimate goal of being able to trace the source of variation through the developmental process.

The special case of transcription in the early embryo

The early embryo has peculiarities and constraints that are particular to this stage of development. For one, in Drosophila, the early embryo is built for developmental speed– for example, the first 14 mitotic divisions in development occur very rapidly, without the presence of cell membranes. The speed in which the embryo develops places physical constraints on transcription and the development of chromatin states, which are not well understood. We wish to understand what these constraints are, what are the mechanisms involved, and how these dynamics play out in development.