Mechanisms of robustness in organogenesis

Cornell University, Ithaca NY

Investigators

Abstract

Mechanisms of robustness in organogenesis Project Summary/Abstract The size and shape of an organ are essential for its function. Developing organs are remarkably robust, meaning that they reproducibly grow to reach the same size and shape in each individual, despite variability in cell growth and division, the inherent stochasticity of gene expression, and environmental fluctuations. The systems-level mechanisms generating this robustness remain largely unknown. When developmental robustness mechanisms in humans are disrupted and these perturbations are not buffered, organ size and shape become variable, resulting in birth defects. My laboratory has focused on deciphering the systems-level mechanisms that yield robustness in organ size and shape. We have established the Arabidopsis sepal, the outermost green leaf-like floral organ, as a model system for studying robustness because we can image the development of living sepals, track the cell lineages, and quantify the cell growth, division, and expression levels of fluorescent markers in the cells throughout the development of the sepal, making it a powerful system for elucidating how cells give rise to the organ size and shape. Our interdisciplinary approach that combines advanced live imaging, genetic engineering, advanced image processing, and computational modeling, uniquely enables us to gain mechanistic insights that reflect both biochemical and mechanical factors of perturbation and robustness. Previously, we isolated the first sepal robustness mutants, and we demonstrated that robustness of size and shape is generated through: (1) precise initiation of organ development, (2) averaging of local fluctuations in cellular growth, and (3) coordination of growth across cell layers of the organ. However, the molecular details of how these mechanisms maintain robustness are largely unknown. Over the next five years we will focus on three complementary and synergistic research areas to further elucidate these robustness mechanisms. First, we will determine how initiating of the development of the organ from the stem cells is robust to stochasticity in hormone signaling. The plant hormone auxin is crucial for organ initiation and our preliminary data suggests auxin signaling is noisy early in development but becomes stabilized into four regions which give rise to four sepals. We will quantify intrinsic versus extrinsic noise in auxin signaling and determine the function of DRMY1 in dampening noise. Second, we will elucidate how organ growth is robust to cellular growth fluctuations. We will test the role of microtubules and intercellular mechanical signals in spatiotemporal averaging of cellular noise to produce robust organ shapes. Third, we will determine how growth coordination mechanisms produce organ shapes that are robust to mechanical conflicts caused by differential growth rates across cell layers. Our work points to a role for the mobile transcription factor ASYMMETRIC LEAVES 2 and microRNAs that can move from cell to cell through plasmodesmata (small pores connecting cells) in coordinating cell growth, which we will test. Our combined results will reveal mechanisms and principles of robustness that together produce highly reproducible organ sizes and shapes.