Positive feedback regulation of wishful thinking shapes bone morphogenetic protein signaling in the follicular epithelium

Morphogenesis is preceded by an extensive gene patterning that is regulated by a small number of signaling pathways. One such pathway, the Bone Morphogenetic Protein (BMP) pathway, is an essential developmental regulator in many organisms throughout Eukarya, including Drosophila melanogaster. An established system to study patterning that is regulated by cell-to-cell signaling is D. melanogaster oogenesis. A two-dimensional monolayer of follicle cells (FCs) surrounds the developing oocyte, becomes patterned and later folds into eggshell structures; this process is regulated, in part, by BMP signaling. While BMP signaling in the FCs is associated with the patterning of the type I receptor, thickveins (tkv), the cooperating type II receptor remains unknown. Here, I aimed to establish its identity. Though previously only reported during embryonic neurogenesis, I found that the type II receptor, wishful thinking (wit), is expressed in an evolutionary conserved pattern in the FCs of species that diverged over 45 million years. Also, WIT is self-regulated by a positive feedback loop, which I demonstrate works to sharpen the BMP signaling gradient. Of importance, null clones of WIT coincide with a cell autonomous loss of BMP signaling, monitored by the phosphorylated form of the intercellular signaling molecule MAD (P-MAD). Loss of WIT has changes the patterning of Broad, a marker for dorsal appendages, affecting eggshell morphology. These results demonstrate an active role for WIT in non-neuronal tissue, and establish WIT as the type II receptor working in concert with TKV during FC patterning.M.S.Includes bibliographical references (p. 16-20)by Robert MarmionIncludes abstrac