Organs must be the right size and shape to fulfill their roles in the animal. Although size is intimately linked to organ function, we know almost nothing about how size control is coupled to organ differentiation during embryonic development. In the proposed work, we focus on how developmental growth and differentiation are coordinated in the Drosophila embryo, an ideal system for revealing the underlying molecular and cellular mechanisms. We have discovered that the nuclear protein Ribbon (Rib) is required for growth and morphogenesis of two distinct organs in the Drosophila embryo and that Rib promotes growth by two different mechanisms in the two tissues. In rib mutants, both salivary gland and tracheal cells are only ~50% the size of WT, and both organs have additional morphological defects. In the salivary gland, Rib binds genes encoding most of the >80 ribosomal protein genes, suggesting that Rib promotes growth in this tissue by increasing the translational capacity of its large secretory cells. In the trachea, Rib binds components of the Tor growth control pathway and other growth genes. We propose the model that Rib couples Tor signaling to FGF signaling to coordinate growth and directional migration in response to both developmental and physiological cues. In this proposal, we test these ideas and we ask how Rib independently regulates morphogenetic factors, specifically those that function at the apical cell surface to control tube elongation. We begin by testing the idea that Rib upregulates ribosomal protein gene expression in the salivary gland to increase translation in these professional secretory cells and we test the model that the small cell size observed in the salivary glands of rib mutants is a ribosome deficiency problem. We then test the model that Rib coordinates growth in the trachea by linking the FGF and Tor signaling pathways to build a system that links growth to migratory cues. We also explore the role of other candidate growth regulators. We determine if a candidate Rib target that is bound by Rib in both the SG and trachea also regulates growth and we determine if Rib affects levels of protein translation. Finally, we ask how Rib coordinates growth and morphogenesis by identifying the co-activators relevant to each process and by characterizing the functions of a subset of target genes linked to cell shape change.

For the tissues and organs in our body to function effectively, they must be the right size and shape and be correctly positioned with respect to other organs, and they must be sufficiently large to fulfill their contributions to our survival and overall fitness. In this proposal, we study how a single regulatory molecule – known as Ribbon - coordinates growth and differentiation of organs during development in the model system of the Drosophila embryo. We propose to learn how Ribbon works with partner proteins to regulate downstream target genes to build organs of the right size and shape to achieve optimal biological function.