Viviane Callier

Body size profoundly affects many aspects of animal biology, yet it remains one of the fundamental unsolved problems of developmental biology. Manduca and Drosophila, two well-studied holometabolous insects and the primary models for the study of size regulation in animals, terminate growth and initiate metamorphosis when larvae attain the critical weight. Attainment of critical weight initiates a hormonal cascade that ultimately triggers a metamorphic molt. Although the hormonal control of molting is well understood, the mechanisms that a larva uses to sense its size and activate the hormonal cascade at a specific size or time are largely unknown. The result is a conspicuous gap in our understanding of the mechanisms that regulate body size.

As larvae grow through an instar, oxygen supply structures are largely fixed, but metabolizing tissues increase in mass. The growth of metabolizing tissues relative to supply structures creates internal hypoxia, and internal hypoxia could be a physiological cue to sense size. I am testing this hypothesis using physiological and molecular-genetic methods in Drosophila. By elucidating the role of hypoxia in the normal regulation of growth and size, this work will also shed light on the mechanisms by which hypoxia regulates the pathological growth of cancer tumors.

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