A Genetic Mechanism Linking Hippo Signaling to Dorsoventral Patterning for Control of Head and Eye Development

Abstract

The integration of growth and patterning in developing tissues is a complex process involving both intrinsic and extrinsic cues. The Hippo pathway, a conserved regulator of organ size, controls growth and patterning in Drosophila, including the development of the eye-antennal imaginal disc into adult structures. Defective Proventriculus (Dve), a SATB1/2 ortholog and K-50 type transcription factor regulates dorsal-ventral (DV) patterning during Drosophila eye development. Dve works with Wingless (Wg) to suppress eye development and promote head cuticle fate, thereby influencing the positioning of eyes and interocular distance. Our study investigates the role of the Hippo effector Yorkie (Yki), and dve in coordinating growth and patterning during eye development, specifically focusing on the regulation of the head cuticle domain. Here we show that Hippo signaling, mediated by Yki, regulates the size of the head cuticle domain and morphogenetic furrow (MF) progression, and that Dve suppresses Yki activity in the dorsal head region. Furthermore, Yki regulates several DV patterning genes like pnr, wg and mirr, to coordinate eye and head development. Mutations in mammalian orthologs of yki, dve, pnr and wg are associated with facial dysmorphia and several developmental disorders. Our studies thus reveal new genetic mechanisms by which growth and patterning are coordinated for head and eye development across species.