Signaling Cascades, Gradients, and Gene Networks in Dorsal/Ventral Patterning

Abstract

Dorsal/ventral (DV) patterning is the process whereby embryonic cells assume different developmental fates as a function of their position along an organism’s DV axis. In the Drosophila embryo, DV patterning begins during oogenesis and is completed during the early stages of embryogenesis. It requires cross-talk between three signal transduction pathways; the epidermal growth factor (EGF) receptor pathway, the Toll (Tl) pathway, and the Decapentaplegic (Dpp)/Short gastrulation (Sog) pathway. The Drosophila oocyte arises from germline stem cells present at the anterior tip of each ovariole. Each ovary contains ∼16 such ovarioles, which consist of a linear series of egg chambers that gradually mature as they move from the anterior to the posterior end of the ovariole. The developing oocyte in each egg chamber is nourished by 15 nurse cells and is surrounded by a monolayer follicle cell epithelium. Gurken (Grk), a transforming growth factor (TGF)-α family protein, is secreted from one side of the developing oocyte close to its anterior end and signals via the endothelial growth factor (EGF) receptor in the adjacent follicle cells. This signal specifies DV polarity in the follicle cell epithelium, which in turn deposits a latent cue in the pervitelline space (the space between the eggshell and the oocyte plasma membrane) on what will become the ventral side of the embryo. After fertilization, activation of the Tl receptor by the ventral cue leads to formation of a ventral to dorsal nuclear concentration gradient of the protein Dorsal (DL). DL is a transcription factor that serves as a morphogen to direct cell fate as a function of position along the DV axis. It does so by regulating ∼50 genes in the blastoderm embryo. Different genes are activated or repressed at different threshold DL concentrations, resulting in multiple domains of gene expression. The action of this gene network specifies the three primary territories along the DV axis; the presumptive mesoderm, the neurogenic ectoderm, and the dorsal ectoderm. Two of the genes regulated by DL, dpp and sog, encode critical components of a second morphogen system required for DV pattern formation. Dpp and Sog form opposing activity gradients along the DV axis, and through these gradients they subdivide the embryo into multiple developmental domains. Loss and gain-of-function genetic analysis carried out in flies, frogs, and fish demonstrate that this role of the Dpp/Sog morphogen system in patterning the DV axis is conserved in both invertebrates and vertebrates.